title: Fine mapping of chromosome 3q22.3 identifies two haplotype blocks in ESYT3 associated with coronary artery disease in female Han Chinese.
abstract: OBJECTIVE
  Genome-wide association study recently identified the chromosome 3q22.3 as a novel locus associated with coronary artery disease (CAD). This study was designed to identify the critical haplotype blocks within this region in Han Chinese populations.
  
  
  METHODS
  We selected 1920 CAD patients and healthy participants from Han Chinese and genotyped 22 single nucleotide polymorphisms (SNPs) spanning 150 kilobases (kb) chromosomal region flanking rs9818870, a SNP associated with CAD at 3q22.3 in Caucasian.
  
  
  RESULTS
  Seven SNPs were found to be strongly associated with CAD in females and clustered in two haplotype blocks of ESYT3 gene. This was validated in two geographically isolated case-control populations. The two blocks were 14 and 25kb long, respectively. In a combined haplotype analysis, the odds ratios (95% confidence interval, permuted P value) were 0.70 (0.58-0.83, 2×10(-5)) and 1.44 (1.20-1.72, 5×10(-5)) for haplotypes TTG and CCA in block 1 as well as 0.73 (0.61-0.87, 3×10(-4)) and 1.35 (1.13-1.62, 0.0013) for haplotypes TCG and CTT in block 2, respectively. ESYT3 was expressed in human lymphocyte, vascular endothelial cell, and smooth muscle cell. The risk factors including gender, obesity, hypertension, diabetes, and hyperlipidemia exhibited strong effects on the genetic contribution to CAD.
  
  
  CONCLUSIONS
  We identified two haplotype blocks of ESYT3 gene in 3q22.3 region that likely harbor functional variants, which cooperate with other risk factors and play a role in the pathogenesis of coronary artery disease in females.
authors: Department of Cardiology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, China.
authors: Feng
authors: F
authors: Jiang
authors: Yumei
authors: Y
authors: Dong
authors: Chong
authors: C
authors: Wu
authors: Xi
authors: X
authors: Yang
authors: Ling
authors: L
authors: Zhao
authors: Jian
authors: J
authors: Guo
authors: Yang
authors: Y
authors: Li
authors: Jie
authors: J
authors: Dong
authors: Gu-Yan
authors: GY
authors: Zheng
authors: Huiqing
authors: H
authors: Cao
authors: Lijuan
authors: L
authors: Jin
authors: Yihong
authors: Y
authors: Ren
authors: Wenli
authors: W
authors: Cheng
authors: Weiyang
authors: W
authors: Li
authors: Xiao-Li
authors: XL
authors: Tian
authors: Xueqi
authors: X
authors: Li
mesh_terms: D000368:Aged; D002681:China; D002893:Chromosomes, Human, Pair 3; D003324:Coronary Artery Disease / Q000208:ethnology / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008214:Lymphocytes / Q000166:cytology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D050857:Synaptotagmins / Q000235:genetics*
chemical_list: C571229:ESYT3 protein, human; D050857:Synaptotagmins