Exploring epistatic relationships of NO biosynthesis pathway genes in susceptibility to CHD

Aim： 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 （0R=1.21, 95% CI： 1.06-1.39, combined P=0.001, Poorr=0.007 and 0R=1.30, 95% CI 1.12-1.50, combined P〈0.001, Pcorr〈0.001, respectively）. Significant two-way SNP-SNP interactions were found between SNP rs2297518 and these two significant polyrnorphisms, affecting the risk of CHD （P〈0.001 for both）. No significant high-order interactions were identified. Conclusion： The results suggested that two-way SNP-SNP interactions of potymorphisms within NO biosynthesis pathway genes contribute to CHD risk.