| Gene | Abstracts | Lvl | Category | Notes |
|---|---|---|---|---|
| BMPR2 | 242 | 9.9 | Experimental evidence of mutations | PMID 10973254 By comparison with in vitro studies, identified defects of BMPR-II in FPPH are predicted to disrupt ligand binding, kinase activity and heteromeric dimer formation. Our data demonstrate the molecular basis of FPPH and underscore the importance in vivo of the TGF-beta signalling pathway in the maintenance of blood vessel integrity SEVERAL REPORTS (vt) |
| ACVRL1 | 42 | 9.9 | Experimental evidence of mutations | Id. 16540754 "Molecular analysis identified mutations in the ACVRL1 gene in 7 of these 9 subjects. Even on exclusion of relatives of the single case with known pulmonary hypertension, 5 of 37 patients (13.5%) still showed values higher than those of controls" Each proband with the ALK1 mutation developed PAH. (vt) |
| BMP1:BMP(52) | 39 | 9.9 | ||
| ENG | 33 | 9.9 | Experimental evidence of mutations | 14684682,15687131,21378382 (mosaicism),26167679 (vt) |
| EDN1 | 18 | 9.9 | Experimental evidence of mutations | Polymorphisms.- 21537392, 22754222, 24529882, 26252367 Review: 24570333 Mutacion en ERA: 25226600 A significant association of EDN1 3A/4A polymorphism (+138 A; rs10478694) (OR-3.485; CI-1.254, 9.999; p=0.013) and EDN1 Lys198Asn polymorphism (G/T, rs5370) (OR-3.378, CI-1.104, 10.582; p=0.03) with IPAH was observed. The genotype analysis of the EDN1 gene polymorphism shows statistically significant differences in patients with PAH compared to healthy individuals. Individuals carrying at least one T allele exhibit a higher relative significant risk to develop HAP. (vt) |
| EIF2AK4 | 18 | 9.9 | Experimental evidence of mutations | 24292273 Mutations in this gene associated with other diseases. PVOD 25512148 we sequenced EIF2AK4 and found a homozygous mutation in all five families: c.3344C>T(p.P1115L). The majority of our patients required early lung transplantation. Hence, this mutation appeared with a more severe phenotype than previously reported for other EIF2AK4 mutations. The finding of this novel mutation is important for genetic counseling and calculation of population recurrence risks. 26699722 Bi-allelic mutations in EIF2AK4 were identified in all patients with a family history of PVOD (n=19) and in seven patients (8.6%) presenting as sporadic PVOD. Pre-symptomatic genetic diagnosis was offered to 272 relatives of heritable PAH patients, identifying mutations in 36.4% of them *** Other disease ? *** It has been found also in heritable PAH patients. (vt) |
| KCNK3 | 16 | 9.9 | Experimental evidence of mutations | Mutated in PAH. 24037626 Recent advancements in gene sequencing methods have facilitated the discovery of additional genes with mutations among those with and without familial PAH (CAV1, KCNK3). HPAH is an autosomal dominant disease characterized by reduced penetrance, variable expressivity, and female predominance. These characteristics suggest that genetic and nongenetic factors modify disease expression, highlighting areas of active investigation. The reduced penetrance makes genetic counseling complex, as the majority of carriers of PAH-related mutations will never be diagnosed with the disease. Our study identified the association of a novel gene, KCNK3, with familial and idiopathic pulmonary arterial hypertension. Mutations in this gene produced reduced potassium-channel current, which was successfully remedied by pharmacologic manipulation. (vt) |
| TGFB1 | 16 | 5.3 | Related but not mutated | Related but not mutated in PAH |
| BMP4 | 15 | 9.9 | Related but not mutated | Related but not mutated. |
| CAV1 | 15 | 9.9 | Experimental evidence of mutations | PMID 23250901 The study highlights the utility of sequencing in identifying 2 novel mutations in CAV1 in human PAH and without involvement in transforming growth factor-_ signaling. Based upon the similarities in the clinical features of these two patients, previous reports of CAV1 mutations in patients with lipodystrophies and pulmonary hypertension, and similar features seen in CAV1 null mice, we conclude that these variants are the most likely cause of one subtype of neonatal onset generalized lipodystrophy syndrome (vt) |
| BMP2 | 13 | 9.9 | Related but not mutated | Related but not mutated. |
| SMAD9 | 12 | 9.9 | Experimental evidence of mutations | SMAD8: 19211612, 19419974 (mice). CONCLUSION: We describe the first mutation in SMAD8 in a patient with IPAH. Our findings suggest the involvement of SMAD8 in the pathogenesis of PAH. More mutations in SMDA9: 21920918, 23590310 Splice site mutation in SMAD4: 21898662 (vt) |
| GDF2 | 11 | 9.9 | Annotation error | BMP9 participates in BMPR2 signalling. (vt) |
| SMAD1 | 11 | 9.9 | Related but not mutated | Relacionado pero no mutado. |
| SLC6A4 | 11 | 9.9 | Unrelated | 16399993 : Variation of the serotonin transporter gene appears unlikely to confer significant susceptibility to pulmonary arterial hypertension. 1914152: SERT polymorphisms are not associated with the risk of PPHTN in patients with advanced liver disease. RECORDS: 10; REPETIDOS: 2; NEOM: 3/8 RELATED BUT NOT MUTATED: 2/8 UNRELATED: 3/8 UNDEFINED: 1/8.- NO ABSTRACT. Significant differences among three groups in the distribution of 5-HTT genotype and allele frequency were present (respectively p = 0.002; p = 0.021) *** Has Controversial Evidence *** (vt) |
| ID1 | 10 | 9.9 | Related but not mutated | Related but not mutated. |
| KCNA5 | 9 | 9.9 | Experimental evidence of mutations | 17267549 :These results suggest that 1) Kv1.5 channels are modulated by various agonists (e.g., nicotine and ET-1); 2) novel SNPs in KCNA5 are present in IPAH patients; and 3) SNPs in the promoter and translated regions of KCNA5 may underlie the altered expression and/or function of Kv1.5 channels in PASMC from IPAH patients. 24936649; CONCLUSIONS: Pathogenic mutations in BMPR2 gene are frequent in patients with idiopathic and associated PAH group I. Mutations in ACVRL1 and KCNA5 are less frequent. The presence of these mutations seems to increase the severity of the disease. 20556823 : Our results provide the first evidence for an association between the KCNA5 rs10744676 variant and PAH associated with SSc. 23270786 :Our data do not support an important role of KCNA5 as an SSc-susceptibility factor or as a PAH-development genetic marker for SSc patients. (vt) |
| SMAD2 | 8 | 9.9 | Related but not mutated | |
| SMAD4 | 8 | 9.5 | Experimental evidence of mutations | mutation confirmed. 15361368; 19211612. The SMAD8 mutant was also unable to interact with SMAD4. The response to BMP was analysed using promoter-reporter activities with SMAD4 and/or ca-ALK3. The transcriptional activation of the SMAD8 mutant was inefficient compared with the SMAD8 wild type. (vt) |
| TBX4 | 8 | 9.9 | Experimental evidence of mutations | Mutated: 23592887 These data indicate that TBX4 mutations are associated with childhood-onset PAH, but that the prevalence of PAH in adult TBX4 mutation carriers is low. (vt) |
| NOS3 | 7 | 5.9 | Genetic alteration in related disease | Some reports tested NOS3 in PAH and did not find mutations, but one report did find so but combined with other polymorphism. So, from several reports it seems that NOS3 is more related to COPD than to IPAH. Polimorfismo en NOS: 14682408 Y 24057178 (HP del grupo 3), 18953956 (COPD) , 22754222 (IPAH). (vt) |
| BMP7 | 7 | 9.8 | Related but not mutated | Related but not mutated. |
| BMPR1A | 7 | 9.9 | Related but not mutated | Related but not mutated. |
| SLPI:ALK1(6) | 7 | 9.9 | Related but not mutated | Related but not mutated. En donde se menciona SLPI? To investigate kindreds presenting with both pulmonary hypertension and HHT. DESCARGADO @ NUEVO PUBTERM. |
| SMAD3 | 6 | 6.6 | Related but not mutated | Related but not mutated. |
| TGFBR1:ALK5(4) | 6 | 8.6 | Annotation error | 19116361 : Collectively, these data are consistent with a role for the activin receptor-like kinase 5 in the progression of idiopathic PAH and imply that strategies to inhibit activin receptor-like kinase 5 signaling may have therapeutic benefit (vt) |
| PTLAH:FPAH(6) | 6 | 9.9 | Annotation error | FPAH refers to familial PAH not to PTLAH gene. (vt) |
| BMPR1B | 5 | 9.9 | Experimental evidence of mutations | PMID 22374147 Two missense mutations (c.479 G>A S160N, c.1176 C>A F392L) in BMPR1B were each identified in 2 IPAH patients. Immunoblot analysis revealed that the BMPR1B F392L protein promoted SMAD8 phosphorylation. (vt) |
| MAPK14:p38 mitogen-activated protein kinase(3) | 4 | 1 | Related but not mutated | activation induced by BMP2, whereas it enhanced p38(MAPK) activation (vt) |
| ACE | 4 | 0.6 | Related but not mutated | Related but not mutated. Polimorfismo: 19332265 .- Patients were genotyped for 5 common polymorphisms in angiotensinogen (AGT), angiotensin-converting enzyme (ACE), cardiac chymase A (CMA1), angiotensin II type 1 receptor (AGTR1), and aldosterone synthase (CYP11B2). |
| IL6:IL-6(3) | 4 | 0 | Unrelated | 17322283 Thus we have shown both in vitro and in vivo a complete negative feedback loop between IL-6 and BMP, suggesting that an important consequence of BMPR2 mutations may be poor regulation of cytokines and thus vulnerability to an inflammatory second hit. (vt) |
| SMAD5 | 4 | 9.9 | Related but not mutated | Related but not mutated. Revision de SMAD: 21898662 |
| SMAD6 | 4 | 9.2 | Related but not mutated | Related but not mutated. Associated with other gene mutations |
| MAPK1:ERK(4) | 4 | 0.5 | Related but not mutated | Related but not mutated. |
| SOX17 | 4 | 8.2 | ||
| TRPC6 | 4 | 6.4 | Experimental evidence of mutations | These results suggest that the -254(C-->G) SNP may predispose individuals to an increased risk of IPAH by linking abnormal TRPC6 transcription to nuclear factor-kappaB, an inflammatory transcription factor Polimorfismo 19380626 This study seems to suggest that c.1-361A > T, c.1-254C > G and c.1-218C > T polymorphisms in TRPC6 gene and c.1166A > C polymorphism in AGTR1 could have a role in the development of this disease. (vt) |
| SLCO1B1 | 3 | 4.3 | Related but not mutated | Not related. |
| CYP1B1 | 3 | 3.5 | Related but not mutated | |
| FLNA | 3 | 5 | Genetic alteration in related disease | 20888935 Here, we report on a male patient aged 6 years presenting with a mosaic nonsense mutation c.994delG within the FLNA gene, PH (vt) |
| SIRT3 | 3 | 5.1 | Experimental evidence of mutations | 25284742: A loss-of-function SIRT3 polymorphism, linked to metabolic syndrome, is associated with PAH in an unbiased cohort of 162 patients and controls (vt) |
| CBLC | 3 | 7.2 | Annotation error | CBLC refer to cobalamin C disease not to CBLC gene. (vt) |
| MMACHC | 3 | 9.9 | Genetic alteration in related disease | 23837176 "Genetic analysis confirmed mutations in MMACHC in all patients". Combined pulmonary hypertension and renal thrombotic microangiopathy in cobalamin C deficiency. 24853097 This patient had isolated pulmonary hypertension and hyperhomocysteinemia which is thought to be an important factor in the pathogenesis of PAH. Genetic analysis identified a novel homozygous mutation (c.484G > T; p.Gly162Trp) in the MMACHC gene. (vt) |
| GREM1:Gremlin-1(1) | 3 | 6.2 | Related but not mutated | |
| SLCO1B3 | 3 | 5.5 | Unrelated | Not related. |
| NOS2 | 3 | 1 | Experimental evidence of mutations | 16813666 : Polymorphisms in the NOS2 gene are associated with transcriptional activity of the NOS2 gene and with susceptibility to SSc-related PAH. 24439467: There are significant differences in the distribution of the NOS2 promotor CCTTT polymorphism between patients with PAH and the healthy population. A minor CCTTT pentanucleotide repeat in the NOS2 gene may increase the risk of developing PAH. *** SSc ? PAH ? or both ? *** (vt) |
| RTN4:Nogo(3) | 3 | 3.8 | Related but not mutated | We showed in SMCs from mice that Nogo-B, a regulator of ER structure, was induced by hypoxia in SMCs of the PAs but not the systemic vasculature through activation of the ER stress-sensitive transcription factor ATF6. Nogo-B induction increased the distance between the ER and mitochondria and decreased ER-to-mitochondria phospholipid transfer and intramitochondrial calcium. 24618539: These data identify several combinatorial modalities that inhibit VSV-G anterograde trafficking and cause mislocalization of BMPR2. (vt) |
| BMP6 | 3 | 5.5 | Related but not mutated | Related but not mutated. Associated with other gene mutations |
| TGFBR2:TbetaR II(2) | 3 | 3.9 | Related but not mutated | Related but not mutated. The expression of type1 TGF-beta receptor (TGFBR) activin-A receptor-like kinase1, TGFBR-2, TGFBR-3 (endoglin), Smad3 and Smad4; as well as TGF-beta signalling and TGF-beta-induced apoptosis, were dramatically reduced in the lungs and PASMC, but not the kidneys, of MCT-treated rodents that developed severe PAH. A disturbed proportion of expression of TGF-beta1 and receptor genes in IPAH patients might be one of the pathogenetic factors of the disease. This study demonstrates the lack of association between these TGFβ receptor gene polymorphisms and SSc-PAH using both sequencing and genotyping methods. (vt) |
| CRP | 2 | 0 | Annotation error | CPR means "C reactive protein". (vt) |
| CBLN2 | 2 | 8.5 | Other genetic evidence | We detected a significant association at the CBLN2 locus mapping to 18q22.3, with the risk allele conferring an odds ratio for PAH of 1.97 (1.59-2.45; P = 7.47 × 10(-10)). CBLN2 is expressed in the lung, and its expression is higher in explanted lungs from individuals with PAH and in endothelial cells cultured from explanted PAH lungs. (vt) |
| CYP2C9 | 2 | 1.4 | Genetic alteration in related disease | 2/2: bosetan pharmacokinetics. Unrelated with PAH. Associated with hepatotoxicity produced by Bosentan in PAH patients. |
| AGT | 2 | 0 | Negative evidence of mutations | No associations were demonstrated for AGT, ACE, CMA1, or CYP11B2. *** Changed *** (vt) |
| AGTR1 | 2 | 1.2 | Experimental evidence of mutations | We studied 247 patients with PAH, comprising 177 with idiopathic PAH (IPAH), 63 with PAH/connective tissue disease (CTD), and 7 with PAH associated with anorexigens. Patients were genotyped for 5 common polymorphisms in angiotensinogen (AGT) Polymorphism: 19332265 The 1166C polymorphism in AGTR1 appears to be associated with a later age at diagnosis in IPAH, suggesting that this pathway could be involved in the biologic variability that is known to occur in PAH. This study seems to suggest that c.1-361A > T, c.1-254C > G and c.1-218C > T polymorphisms in TRPC6 gene and c.1166A > C polymorphism in AGTR1 could have a role in the development of this disease. (vt) |
| EDNRA | 2 | 1.7 | Experimental evidence of mutations | 21773759 Polymorphism: This study analyses the frequency and the potential role of two polymorphisms, the +134del/insA, located in the gene encoding for Endothelin-1 (EDN1), and the His323His in the gene encoding for Endothelin receptor type A (EDNRA) in a cohort of 98 consecutive patients with pulmonary arterial hypertension from two different Cardiology Units. Our findings may suggest a potential link between specific genotypes in the EDNRA gene and susceptibility for PAH. *** Changed *** (vt) |
| EGR1:EGR-1(1) | 2 | 1.9 | ||
| ESR1 | 2 | 0 | Unrelated | Bone morphogenic protein receptor type II expression was downregulated, even in subjects without a mutation in this gene. Women with PAH had higher expression levels of estrogen receptor 1 than normal women. Real-time quantitative PCR confirmed differential expression of the following genes in PAH relative to both normal controls and PH secondary to IPF: a disintegrin-like and metalloprotease with thrombospondin type 1 motif 9, cell adhesion molecule with homology to L1CAM, cytochrome b(558) and beta-polypeptide, coagulation factor II receptor-like 3, A-myb myeloblastosis viral oncogene homolog 1, nuclear receptor coactivator 2, purinergic receptor P2Y, platelet factor 4, phospholamban, and tropomodulin 3. |
| FGF2 | 2 | 0.5 | ||
| FOXF1 | 2 | 5.4 | Genetic alteration in related disease | 26462560 : pulmonary capillary hemangiomatosis. Our data suggest the hypothesis that disruption of the FOXF1 gene enhancer could be a genetic determinant of PCH (vt) |
| BMP10 | 2 | 6.7 | ||
| GNB3 | 2 | 3.9 | Other genetic evidence | The GNB3 C825T polymorphism influences the efficacy of sildenafil in patients with pulmonary hypertension (arterial and thromboembolic). *** In the paper they compare in the subgroups of populations including IPAH (vt) |
| HTR2A:5-HT(2A) receptor(1) | 2 | 1.7 | Unrelated | The various gene polymorphisms and the extent of platelet 5-HT(2A) receptor expression did not influence the hemodynamic variables. (vt) |
| TNC:Tenascin-C(1) | 2 | 1.8 | Related but not mutated | Here we show that pulmonary vascular lesions from patients harboring BMPR2 mutations express high levels of tenascin-C (TN-C), an extracellular matrix glycoprotein that promotes pulmonary artery (PA) smooth muscle cell (SMC) proliferation ... These studies define a novel signaling network relevant to PAH underscored by BMPR2 mutations. (vt) |
| ID2 | 2 | 3.6 | Related but not mutated | 18436795 : Mutations in bone morphogenetic protein type II receptor cause dysregulation of Id gene expression 23771884: Loss of BMPR-II function reduces the induction of Id genes in PASMCs, Id1, and Id3 regulate the proliferation of PASMCs via cell cycle inhibition, an effect that may be exacerbated by inflammatory stimuli. (vt) |
| ID3 | 2 | 4.2 | Related but not mutated | 23771884: Loss of BMPR-II function reduces the induction of Id genes in PASMCs, Id1, and Id3 regulate the proliferation of PASMCs via cell cycle inhibition, an effect that may be exacerbated by inflammatory stimuli. (vt) |
| CXCL8:IL-8(2) | 2 | 0 | Related but not mutated | Signaling pathways |
| JAK2 | 2 | 0.9 | ||
| RHOA | 2 | 1.1 | ||
| MIR21 | 2 | 1.6 | Related but not mutated | 21920918 : Induction of miR-21 and miR-27a may be a critical component of BMP-induced growth suppression, loss of which likely contributes to vascular cell proliferation in HPAH. (vt) |
| MIR27A | 2 | 9.9 | Related but not mutated | 21920918 : Induction of miR-21 and miR-27a may be a critical component of BMP-induced growth suppression, loss of which likely contributes to vascular cell proliferation in HPAH. (vt) |
| SMAD7 | 2 | 2.9 | Related but not mutated | Only mutations in BMPR1B (ALK6) were found. SMAD7 was screen in 43 patients, so "negative evidence of mutations" could be set, however, the study was performed only in 43 individuals. *** (vt) |
| NR3C2:mineralocorticoid receptor(2) | 2 | 2.3 | ||
| NF1 | 2 | 0.8 | Annotation error | Neurofibromastosis type 1 (disease) not to the gene. (vt) |
| NOTCH3 | 2 | 2.8 | Experimental evidence of mutations | Two novel missense mutations (c.2519 G>A p.G840E, c.2698 A>C p.T900P) in NOTCH3 were identified in two PAH patients. (vt) |
| SERPINE1:PAI-1(2) | 2 | 0.5 | Experimental evidence of mutations | 20300292: Our data suggests an association of Hd2/Hd2 genotype, which may lead to the up-regulation of PAI-1 gene leading to increased levels of PAI-1, which is seen in IPAH. among (Spanish) Caucasians, this study does not support the hypothesis that the deletion allele (D) of the ACE gene could be a significant risk factor for VTE, being protective in men. *** This is controversial since one report show association and one report does not *** (vt) |
| PPARG | 2 | 0.6 | Genetic alteration in related disease | 18382765 :"we created mice with targeted deletion of PPARgamma in SMCs and showed that they spontaneously developed PAH" 25986483: A PPARG variant is associated with susceptibility to SSc, consistent with a role of PPAR-γ in the pathogenesis of SSc *** PAH or SSc ? *** (vt) |
| TMEM70 | 2 | 7 | Genetic alteration in related disease | pulmonary arterial hypertension in the newborn (PPHN). PPHN is a life-threatening poorly understood condition with bad prognosis if untreated. Pulmonary hypertension has rarely been reported in mitochondrial disorders and, so far, it has been described in association with TMEM70 deficiency only in one patient. (vt) |
| SMURF1 | 2 | 5 | ||
| PTEN | 2 | 0.4 | Unrelated | 21972386: In conclusion, to our knowledge, this is the first reported case of PAH in a patient with Cowden syndrome. How- ever, the PTEN mutation alone is likely insufficient to lead to PAH; it can be hypothesized that PTEN mutations may be a predisposing factor for the development of PAH, and anorexigen exposure may be a potential trigger. 25610608 : She was diagnosed with Cowden syndrome (CS) 4 years ago, molecularly confirmed by identifying a germline heterozygous mutation in the PTEN gene. ... PTEN mutations are responsible for many of the sporadic cancer syndromes, including CS. (vt) |
| PTGIS:prostacyclin synthase(4) | 2 | 4.3 | Other genetic evidence | 15182267 : CTEPH:chronic thromboembolic pulmonary hypertension. 24605778 : Prostacyclin synthase promoter sequence variants exhibit a range of transcriptional activities. We discovered a significant bias for more active prostacyclin synthase promoter variants in unaffected carriers as compared with affected patients with PAH. *** First discovered in CTEPH, Then tested in PAH and found variants in promoters *** (vt) |
| RAF1 | 2 | 1.5 | Related but not mutated | Mutations in RAF1 are associated with Noonan syndrome and hypertrophic cardiomyopathy. We present two infants with Noonan syndrome and an identical RAF1 mutation, p.Ser257Leu (c.770C>T), who developed severe pulmonary arterial hypertension (PAH) that proved to be fatal. |
| BCL2:Bcl-2(2) | 2 | 0 | Unrelated | |
| CXCL12 | 2 | 1.1 | Unrelated | |
| SP1 | 2 | 0.9 | ||
| SP3 | 2 | 9.9 | ||
| STAT3 | 2 | 0.2 | Unrelated | Not associated. Revision. |
| THBS1 | 2 | 1.6 | Experimental evidence of mutations | Mutated.- 22198906.- We identified THBS1 mutations in three families: a novel missense mutation in two (Asp362Asn), and an intronic mutation in a third (IVS8+255 G/A). Neither mutation was detected in population controls. (vt) Ya descargado: Para revision. 2012 Am J Physiol Lung Cell Mol Physiol-SP1 |
| TNF | 2 | 9.9 | Unrelated | Not associated. 090415: Sin datos de mutacion, polimorfismo o variacion genetica. Sin relevancia para la revision. Srr. |
| TPT1:translationally controlled tumor protein(3) | 2 | 9.9 | Related but not mutated | Relate but not mutated. Mediador de senalizacion de crecimiento endotelial. No se demuestran alteraciones de relevancia para la revision. SILENCIAMIENTO DE TCTP Proteomic screening identified TCTP as a novel mediator of endothelial prosurvival and growth signaling in PAH, possibly contributing to occlusive pulmonary vascular remodeling triggered by EC apoptosis. |
| VIP | 2 | 0.9 | Related but not mutated | Related but not mutated. 090415: Evidencia de interes para la revision. Delecion del Gen VIP lleva al desarrollo espontaneo de PAH aunque no es un modelo de IPA. Opcion terapeutica. |
| ATP13A3 | 2 | 9.7 | ||
| ABCB11 | 2 | 3.1 | Related but not mutated | Bosentan liver injury. (vt) |
| CD4 | 2 | 9.9 | Unrelated | Not associated |
| TCIRG1 | 1 | 0 | Unrelated | Not related |
| KLF2 | 1 | 0 | ||
| RACK1 | 1 | 0 | ||
| POSTN | 1 | 0 | ||
| CES1 | 1 | 0 | ||
| CFL1:cofilin(1) | 1 | 0 | ||
| TOPBP1 | 1 | 0 | Experimental evidence of mutations | Related to PAH 24702692 . WES led to the discovery of TopBP1, a gene whose deficiency may increase susceptibility to small vessel loss in IPAH. (vt) |
| SLCO2B1 | 1 | 0 | Related but not mutated | Related but not mutated. Bosentan. |
| GALNT13 | 1 | 0 | ||
| LRG1:leucine-rich alpha-2-glycoprotein(1) | 1 | 0 | ||
| CMA1 | 1 | 0 | Related but not mutated | Polimorfismos |
| ABCC2 | 1 | 0 | Related but not mutated | |
| COX4I1:COX4(1) | 1 | 0 | ||
| EVC2 | 1 | 0 | ||
| ASB10 | 1 | 0 | ||
| CPS1 | 1 | 0 | ||
| CRHBP | 1 | 0 | Related but not mutated | |
| CRHR1 | 1 | 0 | Genetic alteration in related disease | Variations in CRHR1 are associated with persistent pulmonary hypertension of the newborn. (vt) |
| CSF2:GM-CSF(2) | 1 | 0 | Related but not mutated | loss of BMPR2 induced prolonged phospho-p38 mitogen-activated protein kinase (MAPK) in response to TNF, and this increased GADD34-PP1 phosphatase activity, dephosphorylating eukaryotic translation initiation factor (eIF2α), and derepressing GM-CSF mRNA translation (vt) |
| CSK:c-Src tyrosine kinase(1) | 1 | 0 | Related but not mutated | |
| CDAN1 | 1 | 0 | ||
| CTBP1:C-terminal-binding protein 1(2) | 1 | 0 | Related but not mutated | |
| CCN2:CTGF(2) | 1 | 0 | ||
| CX3CR1 | 1 | 0 | Genetic alteration in related disease | SSc: Polymorphism of the fractalkine receptor CX3CR1 and systemic sclerosis-associated pulmonary arterial hypertension. (vt) |
| CYP2D6 | 1 | 0 | ||
| CYP2E1 | 1 | 0 | ||
| CYP3A4 | 1 | 0 | ||
| CYP3A5 | 1 | 0 | Negative evidence of mutations | Polymorphisms of CYP3A5, SLCO1B1, SLCO1B3, and SLCO2B1 had no significant effect on the disposition of bosentan. *** Negative Evidence? for 46 patients ? (vt) |
| CYP11B2 | 1 | 0 | Negative evidence of mutations | No associations were demonstrated for AGT, ACE, CMA1, or CYP11B2. (vt) |
| CHST13 | 1 | 0 | ||
| CFD:Adipsin(2) | 1 | 0 | ||
| AGER:RAGE(2) | 1 | 0 | ||
| AGL | 1 | 0 | Unrelated | |
| EDN3:ET3(1) | 1 | 0 | Related but not mutated | ET1 and aldosterone stimulated PASMC proliferation of idiopathic PAH more effectively than secondary PAH, whereas Ang II and ET3 failed to activate mitosis in either of the PASMC cell type. The effects of ET1 and aldosterone were blocked by bosentan, an ET type-A/B receptor (ETA/BR) antagonist, and eplerenone, a selective mineralocorticoid receptor (MR) blocker, respectively. Collectively, the functional link between BMP and ET and/or the MR system may be involved in the progress of PASMC mitosis, ultimately leading to the development of clinical PAH. (vt) |
| EIF2S1:eIF2(1) | 1 | 0 | Related but not mutated | These pathways have an intimal function in the PAH-related physiology of smooth muscle proliferation, apoptosis, contraction and cellular stress. Exposure of the cells to ET-1 further increases protein expression within these pathways. Thus our results show changes in signaling pathways as a consequence of PAH and the effect of ET-1 interference on Control and PAH-affected cells. |
| ELF3:imiglucerase enzyme replacement therapy (ERT)(1) | 1 | 0 | ||
| ELN:Elastin(2) | 1 | 0 | Related but not mutated | The absence of extensive pathological cardiac remodeling at the high pressures in these animals suggests a developmental adaptation designed to maintain right-sided cardiac output in a vascular system with altered elastin content. |
| DHRS7C | 1 | 0 | ||
| ENO1:PPH(1) | 1 | 0 | Annotation error | (primary pulmonary hypertension, PPH). (vt) |
| EPAS1:HIF2 alpha(1) | 1 | 0 | Genetic alteration in related disease | From Article: 18650473 These findings confirm that an activating HIF2_ mutation dysregulates erythropoietin production in humans. That HIF2_ plays a central role in regulating erythropoietin is supported by several observations. First, in hepatoma and neuroblastoma cell lines, erythropoietin mRNA was suppressed by siRNA-mediated silencing of HIF2_, but not HIF1_.5 Second, in VhlR/R mice homozygous for a mutation equivalent to that underlying Chuvash polycythemia in humans, there was erythrocytosis in normoxia associated with stabilization of HIF2_, but not HIF1_.6 Third, reduced oxygen delivery to the kidney in rats activates HIF2_, but not HIF1_ in the fibroblasts which produce erythropoietin.7 This report provides the first evidence that genetic HIF activation could cause severe pulmonary hypertension in later life. FULL-TEXT: These findings have several implications. First, there should be a high index of suspicion for pulmonary hypertension in other kindreds with activation of the HIF pathway. Second, inhibitors of PHD enzymes, which are in late stage clinical trials for treatment of anemia, may cause pulmonary hypertension. Third, it raises the possibility that polymorphic variation in HIF2α contributes to the marked differential susceptibility to erythrocytosis, reduced plasma volume, and pulmonary hypertension in humans at high altitude. *** erythrocytosis or PAH ??? *** (vt) |
| EPHX1 | 1 | 0 | Unrelated | |
| ERCC3:TFIIH(2) | 1 | 0 | ||
| ESR2 | 1 | 0 | Unrelated | Hepatopulmonary syndrome (HPS) affects 10%-30% of patients with cirrhosis and portal hypertension and significantly increases mortality. Studies in experimental models indicate that pulmonary angiogenesis contributes to the development of HPS, but pathogenesis in humans is poorly understood. We investigated genetic risk factors for HPS in patients with advanced liver disease. |
| EVC:EVC1(1) | 1 | 0 | ||
| F5:factor V Leiden(1) | 1 | 0 | ||
| F13A1:factor XIIIa(1) | 1 | 0 | ||
| FCGR3A:CD16(1) | 1 | 0 | ||
| FGFR1 | 1 | 0 | Related but not mutated | Conditioned media from PAECs expressing mutant BMPR-II also showed increased activation of luciferase activity in a TGF-_ bioassay. The increased proliferation observed in PASMCs exposed to conditioned media from PAECs expressing mutant BMPR-II was inhibited by neutralizing the antibodies to TGF-_1, or small molecule inhibitors of ALK-5 (SD208) or FGFR1 (SU5402). (vt) |
| FHIT | 1 | 0 | ||
| ZHX2:Raf(2) | 1 | 0 | ||
| FLT4:Vascular Endothelial Growth Factor Receptor 3(1) | 1 | 0 | ||
| ARHGEF18 | 1 | 0 | ||
| ISCU | 1 | 0 | ||
| PPP1R15A:GADD34(1) | 1 | 0 | Related but not mutated | loss of BMPR2 induced prolonged phospho-p38 mitogen-activated protein kinase (MAPK) in response to TNF, and this increased GADD34-PP1 phosphatase activity, dephosphorylating eukaryotic translation initiation factor (eIF2α), and derepressing GM-CSF mRNA translation (vt) |
| SLC7A11:xCT(2) | 1 | 0 | ||
| MTOR | 1 | 0 | ||
| G6PC:glucose-6-phosphatase(1) | 1 | 0 | Related but not mutated | Type 1a glycogen storage disease caused by a deficiency of glucose-6-phosphatase has an estimated incidence of 1 per 100000 with a few reported cases of unexplained severe pulmonary hypertension |
| G6PD | 1 | 0 | ||
| GAD1:Glutamic acid decarboxylase(1) | 1 | 0 | ||
| SETBP1 | 1 | 0 | Unrelated | |
| GATA2 | 1 | 0 | Other genetic evidence | categorized mutations as missense, null, or regulatory to identify genotype-phenotype associations. We identified a broad spectrum of disease: hematologic (MDS 84%, AML 14%, chronic myelomonocytic leukemia 8%), infectious (severe viral 70%, disseminated mycobacterial 53%, and invasive fungal infections 16%), pulmonary (diffusion 79% and ventilatory defects 63%, pulmonary alveolar proteinosis 18%, |
| GBA:GBA1(1) | 1 | 0 | Unrelated | Related with Gaucher disease which is associated with PAH |
| SLC17A5:aspartate aminotransferase(1) | 1 | 0 | Unrelated | |
| NFU1 | 1 | 0 | ||
| GOLGB1:giantin(1) | 1 | 0 | Related but not mutated | Golgi dysfunction was also observed in pulmonary vascular cells in idiopathic PAH (IPAH) in terms of a marked cytoplasmic dispersal and increased cellular content of the Golgi tethers, giantin and p115, in cells in the proliferative, obliterative and plexiform lesions in IPAH. (vt) |
| ANGPT1:angiopoietin-1(1) | 1 | 0 | Related but not mutated | Severe pulmonary hypertension is associated with an increased expression of the angiogenic factor, angiopoietin-1, which shuts off the expression of BMPR1A, a transmembrane protein necessary for BMPR2 signalling |
| CAVIN1:cavin-1(1) | 1 | 0 | ||
| GPT:alanine aminotransferase(1) | 1 | 0 | ||
| GSTP1 | 1 | 0 | Unrelated | Five candidate genes previously associated with COPD susceptibility (EPHX1, SERPINE2, SFTPB, TGFB1, and GSTP1). GSTP1 was assessed in COPD, so in PAH is unknown. (vt) |
| GSTZ1 | 1 | 0 | Genetic alteration in related disease | GSTZ is involved in metabolism of drug used for PAH. PMID: 24038869 We characterized the pharmacokinetics and dynamics of dichloroacetate (DCA), an investigational drug for mitochondrial diseases, pulmonary arterial hypertension, and cancer...the plasma kinetics of DCA in dogs is similar to humans with GSTZ1 polymorphisms that confer exceptionally slow plasma clearance. *** Possible Relation to Treatment *** (vt) |
| GTF2I:TFII-I(1) | 1 | 0 | Related but not mutated | Consequently, cellular defects caused by mutations in BMPRII, found in pulmonary arterial hypertension patients, were compensated through cGKI, supporting the positive action of cGKI on BMP-induced Smad signalling downstream of the receptors. (vt) |
| TMOD3:tropomodulin 3(1) | 1 | 0 | Related but not mutated | Bone morphogenic protein receptor type II expression was downregulated, even in subjects without a mutation in this gene. Women with PAH had higher expression levels of estrogen receptor 1 than normal women. Real-time quantitative PCR confirmed differential expression of the following genes in PAH relative to both normal controls and PH secondary to IPF: a disintegrin-like and metalloprotease with thrombospondin type 1 motif 9, cell adhesion molecule with homology to L1CAM, cytochrome b(558) and beta-polypeptide, coagulation factor II receptor-like 3, A-myb myeloblastosis viral oncogene homolog 1, nuclear receptor coactivator 2, purinergic receptor P2Y, platelet factor 4, phospholamban, and tropomodulin 3. (vt) |
| ANXA1:ANNEXIN A1(1) | 1 | 0 | ||
| HDAC2:Hd2(1) | 1 | 0 | Annotation error | Hd2 refers to Hind III polymorphismsnot to HDAC2 gene. (vt) |
| ANXA5:Annexin V(1) | 1 | 0 | Unrelated | |
| HLA-DPA1 | 1 | 0 | ||
| HLA-DPB1:DPB1(1) | 1 | 0 | ||
| HLA-DRB1:DRB1(1) | 1 | 0 | Other genetic evidence | ID. 17406941: "the HLA-DRB1*0406-DQB1*0302 haplotype is associated with IPAH in Korean patients. These results suggest that certain clinical characteristics of IPAH may be controlled in part by patients' HLA alleles" (vt) |
| HLA-DRB5 | 1 | 0 | ||
| HNRNPC:c.1(1) | 1 | 0 | ||
| APEH:APH(1) | 1 | 0 | ||
| HES1 | 1 | 0 | Negative evidence of mutations | No mutations in HES1 nor HES5 were found. (vt) |
| HSD11B2:11betaHSD2(1) | 1 | 0 | Related but not mutated | Given the fact that BMP-2 and BMP-7 upregulated ETA/BR and MR expression and that BMP-2 decreased 11betaHSD2 (11beta-hydroxysteroid dehydrogenase type 2) levels in PASMCs isolated from idiopathic PAH,.... (vt) |
| HSPA5:GRP78(1) | 1 | 0 | Related but not mutated | , whereas the majority of GRP78/BiP was translocated into the nuclei of cells expressing mutant NOTCH3. Cell proliferation and viability were higher for cells expressing mutant NOTCH3 than for those expressing wild-type NOTCH3. We identified novel NOTCH3 mutations in PAH patients and revealed that these mutations were involved in cell proliferation and viability. NOTCH3 mutants induced an impairment in NOTCH3-HES5 signaling. The results may contribute to the elucidation of PAH pathogenesis. (vt) |
| HSPB2 | 1 | 0 | ||
| ICAM1:ICAM-1(1) | 1 | 0 | ||
| IDH1:IDH(1) | 1 | 0 | Related but not mutated | predicting that isocitrate dehydrogenase (IDH) activity would be altered in PAH |
| APOE | 1 | 0 | Unrelated | |
| IGH | 1 | 0 | ||
| APOH:beta 2-GPI(1) | 1 | 0 | ||
| IL1A:IL-1(2) | 1 | 0 | ||
| IL4:interleukin-4(1) | 1 | 0 | ||
| AQP1 | 1 | 0 | ||
| IL10:IL-10(1) | 1 | 0 | ||
| IL13:IL-13(2) | 1 | 0 | Related but not mutated | Our studies demonstrate that IL-13 contributes to the development of PH via an IL-13Rα2-Arg2-dependent pathway. (vt) |
| INS:insulin(2) | 1 | 0 | Related but not mutated | 22936709: Insulin resistance is present as an early feature of Bmpr2 mutation in mice. Exacerbated insulin resistance through high-fat diet worsened pulmonary phenotype, implying a possible causal role in disease. Impaired glucocorticoid responses may contribute to metabolic defects. (vt) |
| ITGA2B:CD41(1) | 1 | 0 | Unrelated | CD41 was used for selection "Platelet-derived MP (PMP) were defined as CD31(+)/CD41(+) and endothelial-derived MP (EMP) as CD31(+)/CD41(-)" (vt) |
| JUNB:AP-1(2) | 1 | 0 | ||
| MALAT1 | 1 | 0 | ||
| KIT:c-Kit(1) | 1 | 0 | Unrelated | We performed immunohistochemistry to determine the expression of progenitor cell markers (CD133 and c-Kit) |
| ARG2 | 1 | 0 | Related but not mutated | Our studies demonstrate that IL-13 contributes to the development of PH via an IL-13R_2-Arg2-dependent pathway. |
| HES5 | 1 | 0 | Negative evidence of mutations | No mutations in HES1 and HES5 were found. (vt) |
| L1CAM | 1 | 0 | Unrelated | |
| LTBP2 | 1 | 0 | ||
| MIR100:miR-100(1) | 1 | 0 | Related but not mutated | Mir 21, 27 y 100 varia su expresion debido a SMAD9. (vt) |
| MIR145:miR-145(2) | 1 | 0 | Related but not mutated | miR-145 deficiency and anti-miR-mediated reduction resulted in significant protection from the development of PAH. In contrast, miR-143 anti-miR had no effect. Furthermore, we observed upregulation of miR-145 in lung tissue of patients with idiopathic and heritable PAH compared with unaffected control subjects and demonstrated expression of miR-145 in SMC of remodeled vessels from such patients. Finally, we show elevated levels of miR-145 expression in primary PASMCs cultured from patients with BMPR2 mutations |
| MIR17 | 1 | 0 | ||
| MIR214:miR-214(1) | 1 | 0 | ||
| MIR96:miRNA-96(1) | 1 | 0 | ||
| STS:as c(1) | 1 | 0 | ||
| MAOA:MAO-A(1) | 1 | 0 | ||
| MGP | 1 | 0 | Related but not mutated | This gene is associated with Keutel syndrome but it is related with severe Systemic PAH |
| MIF | 1 | 0 | ||
| MMP9:matrix metalloproteinase 9(1) | 1 | 0 | Related but not mutated | Talking about levels of the gene expression. |
| MSX1 | 1 | 0 | Related but not mutated | The transcription factor MSX1, which is known to regulate BMP signaling, was the most upregulated gene (4_) in IPAH patients. These results suggest that IPAH cases have a shared molecular origin, which is closely related to, but distinct from, HPAH. |
| COX1 | 1 | 0 | ||
| CYTB:cytochrome b(1) | 1 | 0 | ||
| MUC6 | 1 | 0 | ||
| MYBL1:A-myb(1) | 1 | 0 | ||
| MYF5 | 1 | 0 | ||
| NCAM1:CD56(1) | 1 | 0 | Annotation error | CD56 was used as marker of NK cells. (vt) |
| NPPB:BNP(1) | 1 | 0 | Annotation error | BNP: Method for measuring not the BNP gene. (vt) |
| NPY6R:PP2(1) | 1 | 0 | Annotation error | Treatment PP2 (vt) |
| NSDHL | 1 | 0 | Unrelated | NSDHL was tested, no positive results, PAH was only a fraction of the symptoms. (vt) |
| KCNK9 | 1 | 0 | ||
| PDE1A | 1 | 0 | ||
| PDGFB | 1 | 0 | Related but not mutated | iPAH patients had higher serum and pulmonary TGF-_ levels and increased ALK1 and ENG expressions in lung tissue, predominantly in PECs. Incubation of the cells with TGF-_ led to Smad1/5/8 phosphorylation and to a production of FGF2, PDGFb and endothelin-inducing PA-SMC growth. Endoglin deficiency protected mice from hypoxic PH. (vt) |
| NOP58 | 1 | 0 | Unrelated | NOP58 was used as reference in the genetic position context. (vt) |
| ENPP1 | 1 | 0 | ||
| PECAM1:CD31(1) | 1 | 0 | Annotation error | CD31 was used as a marker for microparticles. (vt) |
| SERPINE2 | 1 | 0 | Unrelated | In participants with severe COPD, SNPs in EPHX1 and SERPINE2 were associated with hypoxemia in two separate study populations |
| PIK3CD:PI3K(1) | 1 | 0 | ||
| PLAUR:UPAR(2) | 1 | 0 | Genetic alteration in related disease | The UPAR rs344781 gene variant is associated with the SSc vascular phenotype. |
| PRRX1:Prx1(1) | 1 | 0 | ||
| CYCS:cytochrome c(1) | 1 | 0 | Unrelated | Related with apoptosis |
| DNAJC10 | 1 | 0 | ||
| PPA1:PP1(1) | 1 | 0 | Annotation error | GADD34-PP1 refers to gene PPP1R15A. (vt) |
| PPARA:PPAR(2) | 1 | 0 | ||
| PDP1:pyruvate dehydrogenase(2) | 1 | 0 | ||
| CNGB3 | 1 | 0 | ||
| PPIB:CYP b(1) | 1 | 0 | ||
| FEZF2:TOF/TOF MS/MS(1) | 1 | 0 | Annotation error | Refer to time of flight (chromatography) not to the gene. (vt) |
| FIGN:fidgetin(1) | 1 | 0 | ||
| PRKG1:cGKI(1) | 1 | 0 | Related but not mutated | Consequently, cellular defects caused by mutations in BMPRII, found in pulmonary arterial hypertension patients, were compensated through cGKI, supporting the positive action of cGKI on BMP-induced Smad signalling downstream of the receptors. (vt) |
| MAPK3:extracellular signal-regulated kinase 1/2(1) | 1 | 0 | Annotation error | MAPK3 participates in SMAD signalling. (vt) |
| PSMD1:immunoglobulin-like receptors 2DL1/S1 and 3DL1(1) | 1 | 0 | ||
| CD248 | 1 | 0 | ||
| MRTFB:MRTF-B(1) | 1 | 0 | ||
| MRTFA:MRTF-A(1) | 1 | 0 | ||
| HAMP:hepcidin(1) | 1 | 0 | ||
| PTPRN:IA-2(1) | 1 | 0 | ||
| PTX3 | 1 | 0 | Related but not mutated | Pentraxin-3 (PTX3) is a protein mediator of innate immunity that is elevated in the setting of left heart disease and pulmonary arterial hypertension. |
| BAX | 1 | 0 | Related but not mutated | BMP2 decreased serum-induced proliferation and increased the pro-apoptotic Bax/Bcl-2 ratio. (vt) |
| RAC1 | 1 | 0 | Related but not mutated | cytoskeletal defects are common to multiple BMPR2 mutations and are associated with activation of the Rho GTPase, Rac1. (vt) |
| RAD51 | 1 | 0 | ||
| ACE2:angiotensin-converting enzyme 2(1) | 1 | 0 | Unrelated | 090415: Sin datos de mutacion, polimorfismo o variacion genetica. Sin relevancia para la revision. |
| BCL2L1:BclX(1) | 1 | 0 | ||
| RPS6KB1:p70S6K(1) | 1 | 0 | Related but not mutated | These pathways have an intimal function in the PAH-related physiology of smooth muscle proliferation, apoptosis, contraction and cellular stress. Exposure of the cells to ET-1 further increases protein expression within these pathways. Thus our results show changes in signaling pathways as a consequence of PAH and the effect of ET-1 interference on Control and PAH-affected cells. |
| CCL5:RANTES(2) | 1 | 0 | Related but not mutated | 090415: Evidencia de interes para la revision. Expresion RANTES elevada en PAH severa celulas endoteliales fuente de RANTES evidencia de funcion sin alteraciones geneticas. (vt) |
| CCL21 | 1 | 0 | ||
| CX3CL1:fractalkine(2) | 1 | 0 | Genetic alteration in related disease | 16584113 : In conclusion, the increased frequencies of 249I and 280M CX3CR1 alleles in a subgroup of patients with SSc-associated PAH suggest a role for the fractalkine system in the pathogenesis of this condition. Further, the 249I allele might be associated with susceptibility to SSc. (vt) |
| SDHC:pGL3(1) | 1 | 0 | Unrelated | 090415: Sin datos de mutacion, polimorfismo o variacion genetica. Sin relevancia para la revision. Referencia a alteraciones conocidas. |
| SELE:E-selectin(1) | 1 | 0 | Unrelated | 090415: Sin datos de mutacion, polimorfismo o variacion genetica. Sin relevancia para la revision. |
| SRSF2 | 1 | 0 | Unrelated | 090415: Sin datos de mutacion, polimorfismo o variacion genetica. Sin relevancia para la revision. |
| GREM2:gremlin2(1) | 1 | 0 | Related but not mutated | Related but not mutated. 090415: Referencia a alteraciones conocidas. |
| SFTPB | 1 | 0 | Unrelated | Not associated. 090415: Sin datos de mutacion, polimorfismo o variacion genetica. Sin relevancia para la revision. |
| SOD2 | 1 | 0 | Other genetic evidence | 20529999: Tissue-specific, epigenetic SOD2 deficiency initiates and sustains a heritable form of PAH by impairing redox signaling and creating a proliferative, apoptosis-resistant PASMC. SOD augmentation regresses experimental PAH. The discovery of an epigenetic component to PAH may offer new therapeutic targets. *** The study shows Epigenetic modifications. (vt) |
| SRC:c-Src(2) | 1 | 0 | Related but not mutated | Related but not mutated. 090415: Sin datos de mutacion, polimorfismo o variacion genetica. Sin relevancia para la revision. |
| STAT5A | 1 | 0 | Unrelated | Not associated. 090415: Sin datos de mutacion, polimorfismo o variacion genetica. Sin relevancia para la revision. |
| STAT5B | 1 | 0 | Unrelated | Not associated. 090415: Sin datos de mutacion, polimorfismo o variacion genetica. Sin relevancia para la revision. |
| ABCC8 | 1 | 0 | ||
| TAGLN:SM22 alpha(1) | 1 | 0 | Unrelated | Not associated. 090415: Sin datos de mutacion, polimorfismo o variacion genetica. Sin relevancia para la revision. |
| MAP3K7:TAK1(2) | 1 | 0 | ||
| TBX2 | 1 | 0 | Unrelated | Mutated TBX4.- 23592887.- These data indicate that TBX4 mutations are associated with childhood-onset PAH, but that the prevalence of PAH in adult TBX4 mutation carriers is low. 090415: Evidencia de interes para la revision. No se detectaron mutaciones en TBX2. SPS asociado con PAH pediatrica TBX4 |
| TF:transferrin(1) | 1 | 0 | ||
| TFAM | 1 | 0 | ||
| TGFBR3:TGFBR-3(1) | 1 | 0 | Related but not mutated | 17392319:The expression of type1 TGF-beta receptor (TGFBR) activin-A receptor-like kinase1, TGFBR-2, TGFBR-3 (endoglin), Smad3 and Smad4; as well as TGF-beta signalling and TGF-beta-induced apoptosis, were dramatically reduced in the lungs and PASMC, but not the kidneys, of MCT-treated rodents that developed severe PAH. 18097622:A disturbed proportion of expression of TGF-beta1 and receptor genes in IPAH patients might be one of the pathogenetic factors of the disease. (vt) |
| THBS4 | 1 | 0 | ||
| TLR2 | 1 | 0 | Unrelated | Not associated. 090415: Sin datos de mutacion, polimorfismo o variacion genetica. Sin relevancia para la revision. |
| TNFAIP3 | 1 | 0 | Unrelated | Not associated. 090415: Sin datos de mutacion, polimorfismo o variacion genetica. Sin relevancia para la revision/ duplicacion. |
| SFTPA2:sPA(1) | 1 | 0 | ||
| UCP2 | 1 | 0 | ||
| VEGFA:VEGF(2) | 1 | 0 | ||
| VHL | 1 | 0 | Unrelated | Not associated. 090415: Evidencia de interes para la revision, pero no de relevancia. Von Hippel-Lindau esta asociado con factor de inductor de hipoxia, alterando fisiologia vascular, asociado a enfermedad VHL, correspondencia al editor. |
| XBP1 | 1 | 0 | ||
| LRP8 | 1 | 0 | ||
| CXCR4 | 1 | 0 | Unrelated | Not associated. 090415: Sin datos de mutacion, polimorfismo o variacion genetica. Sin relevancia para la revision. |
| ATP8B4 | 1 | 0 | ||
| COL18A1 | 1 | 0 | Unrelated | Not associated |
| GDF5 | 1 | 0 | Unrelated | Not associated. |
| CANX:calnexin(1) | 1 | 0 | ||
| CASP3:caspase-3(1) | 1 | 0 | Unrelated | Caspase 3 was used to measure apoptosis. (vt) |
| CASP8:caspase-8(1) | 1 | 0 | Unrelated | Not associated 090415: Sin datos de mutacion, polimorfismo o variacion genetica. Sin relevancia para la revision. |
| CASP9:caspase-9(1) | 1 | 0 | Unrelated | Not associated 090415: Sin datos de mutacion, polimorfismo o variacion genetica. Sin relevancia para la revision. |
| CRACR2A:EFCAB4B(1) | 1 | 0 | ||
| USO1:p115(1) | 1 | 0 | ||
| PDE5A:PDE-5(2) | 1 | 0 | ||
| CBL | 1 | 0 | ||
| PROM1:CD133(1) | 1 | 0 | Unrelated | Not associated 090415: Marcador celular.- Sin datos de mutacion, polimorfismo o variacion genetica. Sin relevancia para la revision. |
| ACVR1:ALK2(2) | 1 | 0 | Related but not mutated | ALK2 knockdown has an effect. (vt) |
| KCNQ4:K(v)7.4(1) | 1 | 0 | ||
| ACVR2A:ActR-II(1) | 1 | 0 | Unrelated | Not associated. 090415: Sin datos de mutacion, polimorfismo o variacion genetica. Sin relevancia para la revision. |
| BMP15 | 1 | 0 | ||
| CD19 | 1 | 0 | ||
| ADIPOQ:adiponectin(1) | 1 | 0 | ||
| COX5A | 1 | 0 | ||
| NCR1:NKp46(1) | 1 | 0 | Related but not mutated | Related but not mutated. 090415: Evidencia de interes para la revision, pero no de relevancia. Referencia a alteraciones conocidas. |
| CHST3 | 1 | 0 | ||
| CD34 | 1 | 0 | ||
| CD44 | 1 | 0 |
The data shown here is supplementary for the research publication A systematic review of genetic mutations in pulmonary arterial hypertension. Gerardo Garcia-Rivas, Carlos Jerjes-Sánchez, David Rodriguez, José Garcia-Pelaez and Victor Trevino. PMID:28768485.
Abstract
Background: Pulmonary arterial hypertension (PAH) is a group of vascular diseases that produce right ventricular dysfunction, heart failure syndrome, and death. Although the majority of patients appear idiopathic, accumulated research work combined with current sequencing technology show that many gene variants could be an important component of the disease. However, current guidelines, clinical practices, and available gene panels focus the diagnosis of PAH on a relatively low number of genes and variants associated with the bone morphogenic proteins and transforming Growth Factor-β pathways, such as the BMPR2, ACVRL1, CAV1, ENG, and SMAD9.
Methods: To provide an expanded view of the genes and variants associated with PAH, we performed a systematic literature review. Facilitated by a web tool, we classified, curated, and annotated most of the genes and PubMed abstracts related to PAH, in which many of the mutations and variants were not annotated in public databases such as ClinVar from NCBI. The gene list generated was compared with other available tests. Results: Our results reveal that there is genetic evidence for at least 30 genes, of which 21 genes shown specific mutations. Most of the genes are not covered by current available genetic panels. Many of these variants were not annotated in the ClinVar database and a mapping of these mutations suggest that next generation sequencing is needed to cover all mutations found in PAH or related diseases. A pathway analysis of these genes indicated that, in addition to the BMP and TGFβ pathways, there was connections with the nitric oxide, prostaglandin, and calcium homeostasis signalling, which may be important components in PAH.
Conclusion: Our systematic review proposes an expanded gene panel for more accurate characterization of the genetic incidence and risk in PAH. Their usage would increase the knowledge of PAH in terms of genetic counseling, early diagnosis, and potential prognosis of the disease.
Keywords: Genetic panel, Germ-line mutation, Heterozygote detection, Systematic review
Abstract
Background: Pulmonary arterial hypertension (PAH) is a group of vascular diseases that produce right ventricular dysfunction, heart failure syndrome, and death. Although the majority of patients appear idiopathic, accumulated research work combined with current sequencing technology show that many gene variants could be an important component of the disease. However, current guidelines, clinical practices, and available gene panels focus the diagnosis of PAH on a relatively low number of genes and variants associated with the bone morphogenic proteins and transforming Growth Factor-β pathways, such as the BMPR2, ACVRL1, CAV1, ENG, and SMAD9.
Methods: To provide an expanded view of the genes and variants associated with PAH, we performed a systematic literature review. Facilitated by a web tool, we classified, curated, and annotated most of the genes and PubMed abstracts related to PAH, in which many of the mutations and variants were not annotated in public databases such as ClinVar from NCBI. The gene list generated was compared with other available tests. Results: Our results reveal that there is genetic evidence for at least 30 genes, of which 21 genes shown specific mutations. Most of the genes are not covered by current available genetic panels. Many of these variants were not annotated in the ClinVar database and a mapping of these mutations suggest that next generation sequencing is needed to cover all mutations found in PAH or related diseases. A pathway analysis of these genes indicated that, in addition to the BMP and TGFβ pathways, there was connections with the nitric oxide, prostaglandin, and calcium homeostasis signalling, which may be important components in PAH.
Conclusion: Our systematic review proposes an expanded gene panel for more accurate characterization of the genetic incidence and risk in PAH. Their usage would increase the knowledge of PAH in terms of genetic counseling, early diagnosis, and potential prognosis of the disease.
Keywords: Genetic panel, Germ-line mutation, Heterozygote detection, Systematic review
