title: Exploring epistatic relationships of NO biosynthesis pathway genes in susceptibility to CHD.
abstract: OBJECTIVE
  To assess the epistatic relationships of nitric oxide (NO) biosynthesis pathway genes in susceptibility to coronary heart disease (CHD).
  
  
  METHODS
  A total of 2142 subjects enrolled in two case-control studies was genotyped for 7 single-nucleotide polymorphisms (SNP) within NO biosynthesis pathway genes using TaqMan assays. The association analyses were performed at both SNP and haplotype levels. Two-way SNP-SNP interactions and high-order interactions were tested using multiple unconditional logistic regression analyses and generalized multifactor dimensionality reduction (GMDR) analyses, respectively.
  
  
  RESULTS
  Two alleles (rs1049255*C and rs841*A) were identified that were significantly associated with increased risk of CHD after adjusting for all confounders (OR=1.21, 95% CI: 1.06-1.39, combined P=0.001, P(corr)=0.007 and OR=1.30, 95% CI 1.12-1.50, combined P<0.001, P(corr)<0.001, respectively). Significant two-way SNP-SNP interactions were found between SNP rs2297518 and these two significant polymorphisms, affecting the risk of CHD (P<0.001 for both). No significant high-order interactions were identified.
  
  
  CONCLUSIONS
  The results suggested that two-way SNP-SNP interactions of polymorphisms within NO biosynthesis pathway genes contribute to CHD risk.
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, China.
authors.forename: Yuan-chao
authors.initials: YC
authors.lastname: Tu
authors.forename: Hu
authors.initials: H
authors.lastname: Ding
authors.forename: Xiao-jing
authors.initials: XJ
authors.lastname: Wang
authors.forename: Yu-jun
authors.initials: YJ
authors.lastname: Xu
authors.forename: Lan
authors.initials: L
authors.lastname: Zhang
authors.forename: Cong-xin
authors.initials: CX
authors.lastname: Huang
authors.forename: Dao-wen
authors.initials: DW
authors.lastname: Wang
mesh_terms: D000368:Aged; D000483:Alleles; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D002681:China; D003327:Coronary Disease / Q000235:genetics*; D004843:Epistasis, Genetic; D005260:Female; D006136:GTP Cyclohydrolase / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D019255:NADPH Oxidases / Q000235:genetics*; D009569:Nitric Oxide / Q000096:biosynthesis* / Q000235:genetics; D020641:Polymorphism, Single Nucleotide
chemical_list: D009569:Nitric Oxide; D019255:NADPH Oxidases; C086986:CYBA protein, human; D006136:GTP Cyclohydrolase