SESSION TITLE: Pulmonary Hypertension Posters I
SESSION TYPE: Poster Presentations
PRESENTED ON: Saturday, March 22, 2014 at 01:15 PM - 02:15 PM
PURPOSE: Pulmonary arterial hypertension (PAH; OMIM 178600) is a progressive vascular disorder characterized by pulmonary vascular resistance increase, vascular remodelling and right heart failure. In pulmonary arteriolar smooth muscle cells (PASMC), canonical TRP channels (TRPC) are involved in agonist-mediated pulmonary vasoconstriction and mitogen-mediated cell proliferation. TRPC6 is an isoform and a critical contributor to the elevated [Ca2+]cyt in PAH PASMC.
METHODS: We included 41 PAH patients and 50 controls. The DNA extraction was performed with Qiagen FlexiGene DNA kit. Using specifically designed primers we amplified by PCR and sequenced the 5-untraslated region of TRPC6.
RESULTS: Three SNPs (-361A>T, -254C>G and -218C>T) in TRPC6 gene were analyzed in Promoter Region of TRPC6. Compared the genotype frequencies with normal subjects and patients with PAH, we obtain statistically significant differences for the three SNPs between the two groups (p=0.049, p>0.001 and p>0.001). The RR of developing PAH in patients with three SNPs is 15.36; IC 95%; p<0.001. These 3 SNPs are present in 50% of patients with idiopathic PAH, giving them a more severe phenotype. In patients with PAH associated with connective tissue and other groups, the 3 SNP are present in the 29% and 36% of patients, respectively, and the phenotype is similar in both groups.
CONCLUSIONS: In conclusion, the 3 SNPs in TRPC6 gene may predispose individuals to an increased risk of developing of PAH by linking abnormal TRPC6 transcription. These SNPs may link the inflammatory response to upregulation of TRPC6 and ultimately alterations in the pulmonary vasculature. All the 3 SNPs produce a more severe phenotype in patients with idiopathic PAH.
CLINICAL IMPLICATIONS: The main clinical implication of this study is that this polymorphism may be used as a method of diagnosis or prognosis of patients with PAH.
DISCLOSURE: The following authors have nothing to disclose: Guillermo Pousada, Adolfo Baloira, Carlos Vilariño, Diana Valverde
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