Association of the OAS3 rs1859330 G/A genetic polymorphism with severity of enterovirus-71 infection in Chinese Han children.

Abstract

The 2'5'-oligoadenylate synthetase (OAS) is an interferon (IFN)-induced protein that plays an important role in the antiviral action of IFN, with OAS3 being one of the four OAS classes (OAS1, OAS2, OAS3, OASL). The effect of OAS on several infectious viral diseases has been reported; however, a study of the effect of OAS3 on enterovirus 71 (EV71) is lacking. The purpose of this study was to evaluate the association of the OAS3 rs1859330 G/A genetic polymorphism with susceptibility and severity of EV71 infection. We investigated 370 Chinese Han children with hand-foot-mouth disease (HFMD) (214 of which were mild cases while 156 were severe). An improved multiplex ligation detection reaction (iMLDR) technique was carried out to examine the genotype. The AA genotype distribution (p = 0.002) and A allele frequency (OR = 1.83, 95% CI 1.32-2.52, p < 0.001) of OAS3 rs1859330 in severe cases were significantly higher than in mild cases. When comparing the different genotypes in EV71-infected patients, there were statistical differences in relation to rash (p = 0.03), oral ulcers (p = 0.005), pathologic reflex (p = 0.003), WBC counts (p = 0.032), CRP (p = 0.024), BG concentrations (p = 0.029), ALT (p = 0.02), and EEG (p = 0.019). However, there were no differences in relation to age, gender, AST, CK-MB, CT/ MRI, as well as some symptoms and signs (e.g. duration of fever (days), headache, convulsions, consciousness disturbance, paralysis, sign of meningeal irritation). In the cerebrospinal fluid (CSF) of severe cases, there were no differences in the levels of white cells, protein, glucose, chloride, lymphocytes and monocytes between the different genotypes. The plasma levels of IFN-γ in EV71-infected patients were significantly higher than in the control group (p < 0.01). IFN-γ concentrations in severe cases were lower in A allele carriers (AA+GA) (118.5 ± 12.6pg/mL) than in GG homozygotes (152.6 ± 56.3pg/mL p < 0.05). These findings suggest that the OAS3 rs1859330 G/A genetic polymorphism is associated with the severity of EV-71 infection, and that the A allele is a risk factor for the development of severe EV71 infection.