Endothelial nitric oxide synthase gene -922A > G, -786 T > C, 4b/4a, and 894 G > T variants and premature coronary artery disease: An association study with haplotype analysis

Background: Endothelium nitric oxide (eNO) deficiency may lead to premature coronary artery disease (pCAD). This defect could be due to the effect of some eNOS gene variants on its gene expression. The aim of the study: The aim of this study is to investigate the association between four eNOS gene variants, independently and as four-locus haplotypes, with pCAD in the southern population of Iran. Methods: One hundred fifty pCAD patients and 150 age and sex-matched controls were enrolled in this study. Polymerase chain reaction and PCR restriction fragment length polymorphism methods were used for 4a/4b variable number tandem repeat and "-922A/G, -786T/C, 894G/T" single nucleotide polymorphisms, respectively. Results: The results indicated that genotype frequencies of four studied variants between case and control groups were different significantly (p < .05) except for GG (-922A/G), CC (-786 T/C), GT and TT (894G/T) genotypes (p > .05). Likewise, all of the studied four mutant alleles (-922G, -786C, 894 T, and 4a) were associated with increased risk of pCAD (p < .05, OR = 1.966, OR = 3.107, OR = 2.21, OR = 1.650, respectively). H4 (bGCT) and H7 (aGCG) haplotypes were significantly associated with pCAD which introduced susceptible haplotypes (p < .01, p < .0001, respectively). However, H1 (bATG) as a protective haplotype, was in a significant negative association with pCAD (P < .0001). Conclusions: In conclusion, this study suggested three novel four-locus haplotypes of eNOS gene variants that could be in association with pCAD in the southern population of Iran.