RT Journal Article
SR Electronic
T1 Molecular study of genetic modifiers in patients with pulmonary arterial hypertension
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP P2363
VO 44
IS Suppl 58
A1 Guillermo Pousada
A1 Adolfo Baloira
A1 Diana Valverde
YR 2014
UL http://erj.ersjournals.com/content/44/Suppl_58/P2363.abstract
AB Pulmonary arterial hypertension (PAH; OMIM 178600) is a disorder characterized by pulmonary vascular resistance increase, vascular remodelling and right heart failure. There is variable phenotypic expression of PAH, likely related to environmental and genetic modifiers. Studies have implicated the serotonin transporter, endothelin, nitric oxide sintase, angiotensine, and others as genetic modifiers. The aim of this work was to analyse several polymorphisms in SERT, EDN1, NOS2 and AGTR1 genes in patients with PAH.We included 55 PAH patients and 52 controls. The analysis was performed by PCR and sequencing.We found statistically differences between patients and controls for the following genes; EDN1 (p=0.009), the genotype GT appears in 62% of patients and in 40% of controls, NOS2 (p<0.001), patients have less repetitions than controls in CCTTT microsatellite, and AGTR1 (p<0.001), the genotype AC appears in 60% of patients and in 20% of controls. On the contrary, the SERT gene don´t show differences (p=0.956). For the genotype/phenotype correlation we don´t found differences for carriers of changes in EDN1 and NOS2 genes. The statistical analysis showed significant differences in age of diagnosis (p=0.043), for the SERT gene, and systolic pulmonary pressure (p=0.037), cardiac index (p=0.012) and PAH subtypes (IPAH vs APAH) (p=0.028), for the AGTR1 gene.In conclusion, HAP is a heterogeneity disease and the genetic modifiers may predispose individuals to an increased risk of developing of PAH, producing a more severe phenotype in patients with PAH. Perhaps the combination of more than one modifier increases the risk of develop it and might be involved in the low penetrance of this disease.