Abstract 17494: Exome Sequencing Reveals a Novel SNP in TRPC6 in Pulmonary Arterial Hypertension

Introduction: The Ca2+ sensing receptor TRPC6 has been reported to promote pulmonary vascular disease. A functional promoter SNP (-254(C/G) has also been previously reported to be over-represented in patients with PAH. We hypothesized that there may be other novel SNPs associated with PAH in TRPC6. Methods: Whole-exome sequencing (WES) was performed on lung tissue DNA collected at the time of transplant or autopsy from 12 patients with PAH (WHO Group I). Standard BWA, SAMTOOLS, and GATK protocols were used to analyze WES data. Filtered SNPs on were compared against 1000 genomes and dbSNP databases for case-control analysis. In a separate PAH cohort (n=47, WHO Group I) with available clinical data, genotyping of a top candidate SNP, rs191383391, was performed via PCR. Association between genotype [wild-type (GG), homozygous recessive (TT)] and clinical phenotypes including right heart catheterization-defined pulmonary vascular resistance (PVRi), cardiac index (CI), cardiac MRI-defined right ventricular eje...