Interplay between polymorphisms in the endothelial nitric oxide synthase (eNOS) gene and metabolic syndrome in determining the risk of ischemic stroke in Koreans

• We investigated the association of four eNOS polymorphisms with ischemic stroke.
• The 894TT and 894GT + TT were significantly higher in stroke patients.
• A positive association between − 786T > C and MetS was observed.
• We report that eNOS variants may contribute to MetS and stroke pathogenesis.

BackgroundEndothelial nitric oxide synthase (eNOS) gene variants are known to play a role in atherosclerotic development. However, whether interplay between eNOS polymorphisms and metabolic syndrome (MetS) affects ischemic stroke (IS) risk has yet to be discovered. We investigated whether the combined effects of eNOS polymorphisms and MetS influence ischemic stroke risk in Koreans.MethodsWe genotyped the eNOS − 922A > G, − 786T > C, 4a4b, and  894G > T polymorphisms in 531 IS cases and 502 controls using polymerase chain reaction-amplified DNA. We then investigated whether the presence of MetS and the number of MetS risk factors worked with eNOS polymorphisms to influence IS risk.ResultsIS patients had a significantly higher prevalence of MetS than controls [adjusted odds ratio (AOR) = 2.943, 95% confidence interval (CI), 2.256–3.840, P < 0.0001], and MetS prevalence did not differ between stroke subtypes. The 894GT + TT genotypes were positively associated with IS (AOR = 1.670, 95% CI, 1.208–2.308, P = 0.002), and the − 786TC + CC genotypes showed co-morbidity with MetS (AOR = 1.448, 95% CI, 1.401–2.015, P = 0.028). Among subjects with three or more MetS risk factors, the highest AOR value (28.490, 95% CI, 3.162–256.688) was observed for the eNOS − 786TC + CC genotypes.ConclusionsThe eNOS 894T allele and interplay between the eNOS − 786C allele and MetS may predispose Koreans to IS.