• Yufeng Zhuo, Qingchun Zeng, Peng Zhang, Guoyang Li, Qiang Xie, and Ying Cheng.
• Department of Cardiology, Panyu Hexian Memorial Hospital, Guangzhou, China. yufengzhuo06@163.com.
• Yonsei Med. J. 2017 Mar 1; 58 (2): 305311305-311.

PurposeEvidence on the contribution of genes to the hereditary predisposition to pulmonary arterial hypertension (PAH) is limited.Materials And MethodsIn 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.ResultsWe found that the rs833061T>C polymorphism was significantly associated with PAH risk, while the other single nucleotide polymorphisms 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.ConclusionOur findings suggest that the functional polymorphism rs833061T>C in VEGF gene promoter modulates VEGF expression and may be a valuable biomarker for predicting PAH susceptibility.

35 keywords...

hide…