Genotype polymorphisms of GGCX, NQO1, and VKORC1 genes associated with risk susceptibility in patients with large-artery atherosclerotic stroke

Abstract Background γ-Glutamyl carboxylation, a reaction essential for the biosynthesis of vitamin K-dependent coagulation factors, requires the participation of the γ-glutamyl carboxylase ( GGCX ), vitamin K epoxide reductase ( VKORC1 ), and NAD(P)H:quinone oxidoreductase ( NQO1 ). We evaluated the role of these genotype polymorphisms in patients with large-artery atherosclerotic stroke. Methods In this hospital-based case–control study, 117 patients who were categorized as having large-artery atherosclerotic stroke and 115 age- and gender-matched controls were recruited. Genotyping determination for the GGCX1 (Gln325Arg), NQO1 (Pro187Ser), and VKORC1 (rs9923231) polymorphisms was performed. The associations of genotype with ischemic stroke (IS) risk were examined. Results A higher genotypic frequency of NQO1 C609T was found in the controls than in the patients, manifesting a 0.47-fold risk reduction in IS (95% CI = 0.25–0.87). A tendency toward a reduced IS risk was statistically significant in those subjects who carried a greater number of the NQO1 , GGCX , and VKORC1 polymorphisms (aOR = 0.58, P trend  = 0.005). The synergistic effect of multiple genes on risk reduction was more significant in a subset of patients who were not alcoholics and who were non-smokers ( P Conclusions Compartmentation of coagulation factor metabolism may account for the preferential role of NQO1 , GGCX , and VKORC1 polymorphisms to lower the risk for large-artery atherosclerotic stroke.