title: VEGF Promoter Polymorphism Confers an Increased Risk of Pulmonary Arterial Hypertension in a Chinese Population.
abstract: OBJECTIVE
  Evidence on the contribution of genes to the hereditary predisposition to pulmonary arterial hypertension (PAH) is limited.
  
  
  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 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.
  
  
  CONCLUSIONS
  Our 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.
authors.affiliation: Department of Cardiology, Panyu Hexian Memorial Hospital, Guangzhou, China. yufengzhuo06@163.com.
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Zhuo
authors.affiliation: Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Qingchun
authors.initials: Q
authors.lastname: Zeng
authors.affiliation: Department of Cardiology, Panyu Hexian Memorial Hospital, Guangzhou, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Department of Respiratory Medicine, Panyu Hexian Memorial Hospital, Guangzhou, China.
authors.forename: Guoyang
authors.initials: G
authors.lastname: Li
authors.affiliation: Department of Cardiology, Panyu Hexian Memorial Hospital, Guangzhou, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Xie
authors.affiliation: Department of Cardiology, Panyu Hexian Memorial Hospital, Guangzhou, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Cheng
mesh_terms: D000483:Alleles; D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D002681:China / Q000453:epidemiology; D065627:Familial Primary Pulmonary Hypertension / Q000208:ethnology / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007963:Leukocytes, Mononuclear; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger; D012189:Retrospective Studies; D012306:Risk; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*
chemical_list: D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A
keywords: VEGF; polymorphism; pulmonary arterial hypertension; susceptibility