Impact of endothelial nitric oxide synthase gene polymorphism on severity of enterovirus 71-infection in Chinese children

Abstract

ObjectivesGenetic polymorphism G894T on the endothelial nitric oxide synthase (eNOS) gene has been reported as a susceptibility factor in a number of diseases, but evidence of its effect on enterovirus 71 (EV71) infection is lacking. This study investigated the possible association between this polymorphism (rs1799983) and disease severity in Chinese children with EV71 infection. Design and methods185 children with EV71 infection (83 with severe and 102 with mild disease) and 234 control healthy children underwent testing with polymerase chain reaction–restriction fragment length polymorphism (PCR–RLFP) to detect G894T polymorphism. In addition, plasma levels of nitric oxide (NO), interleukin 1 beta (IL-1β), interleukin 6 (IL-6), and tumor necrosis factor-alpha (TNF-α) and serum eNOS activity were measured according to genotype. ResultsThe presence of GT+TT genotypes and T allele were associated with severe cases compared to genotype GG (OR 2.5, 95% CI 1.2–5.3, P=0.017) and G (OR 2.4, 95% CI 1.2–4.8, P=0.011). Furthermore, in EV71 encephalitis, GT+TT genotype and T allele were also more frequent than GG and G (P<0.05). The NO level and eNOS activity in T carriers (GT+TT) (84.3±2.5μmol/L and 14.4±1.8U/mL) were significantly less compared to in G carriers (GG) (92.0±1.5μmol/L and 19.1±1.7U/mL, P<0.001). But T carriers had higher plasma levels of IL-1β, IL-6, and TNF-α than people without a T allele (P<0.001), and a significant negative correlation was observed between NO and cytokine levels. ConclusionThe results indicate that carrying the T allele of the eNOS G894T gene polymorphism was associated with EV71 infection, and could be a susceptibility factor in the development of EV71 infection in Chinese children.