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Yufeng Zhuo,Qingchun Zeng,Peng Zhang,Guoyang Li,Qiang Xie,Ying Cheng 연세대학교의과대학 2017 Yonsei medical journal Vol.58 No.2
Purpose: Evidence on the contribution of genes to the hereditary predisposition to pulmonary arterial hypertension (PAH) is limited. Materials and Methods: In this study, we hypothesized that single nucleotide variants in vascular endothelial growth factor (VEGF) gene may alter gene function and expression and may be associated with PAH risk. Five putatively functional loci (rs699947C>A and rs833061T>C in the promoter, rs3025040C>T, rs10434G>A and rs3025053G>A in the 3’-UTR) in the VEGF gene were genotyped and analyzed in a retrospective study of 587 patients with PAH and 736 healthy subjects from southern China. Results: We found that the rs833061T>C polymorphism was significantly associated with PAH risk, while the other single nucleotidepolymorphisms were not. Compared to carriers with TT genotype, those with rs833061C variant genotype (CT/CC) had an increased risk of PAH (odds ratio=1.47, 95% confidence interval=1.18–1.83, p=0.001). Functional assays indicated that CT/CC variant genotype had significantly higher mRNA levels of VEGF in peripheral blood mononuclear cells than TT genotype (p=0.021). Luciferase reporter assay indicated that having a C allele conferred a significantly higher transcription activity than that with a T allele. Conclusion: Our findings suggest that the functional polymorphism rs833061T>C in VEGF gene promoter modulates VEGF expressionand may be a valuable biomarker for predicting PAH susceptibility.
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