Association analysis of polymorphisms in OAS1 with susceptibility and severity of hand, foot and mouth disease.

Abstract

Hand, foot and mouth disease (HFMD) is a common childhood illness that mainly affects Asian children under the age of 5years. Human enterovirus 71 (EV71) and coxsackievirus A16 (CA16) are the most common pathogens of HFMD. It is imperative that the susceptible population is screened early and that the severe illness population can be identified via genetic variation detection in children. Four single-nucleotide polymorphisms (SNP) [2'-5'-oligoadenylate synthetase1 (OAS1) rs10774671, selectin P ligand (SELPLG) rs2228315, scavenger receptor class B member 2 (SCARB2) rs41284767 and interleukin 28B (IL28B) rs12979860] were determined by Taqman assays in 333 HFMD samples and 163 control samples. The rs2228315, rs41284767 and rs12979860 polymorphisms did not differ significantly between HFMD patients and the controls, but the prevalence of the rs10774671 polymorphism was significantly different between the control children and children infected with CA16 (GG genotype vs. AA+AG genotype, P<0.05). Children with the GG genotype were more susceptible to CA16-type HFMD. Furthermore, the rs10774671 genotype distribution was clearly different between children with severe HFMD and those with mild HFMD [P<0.05, OR 0.240, 95% CI (0.071-0.809)]. HFMD children with the AA+AG genotype were more likely to progress to encephalitis than were those with the GG genotype. Plasma γ-interferon (IFN) expression levels among control children and the mild and severe HFMD children were detected by ELISA. Those with mild HFMD had higher γ-IFN expression levels compared with those with severe HFMD (P<0.05). In addition, there is a significant correlation between γ-IFN levels and OAS1 rs10774671 SNP, as analysed by linear correlation assay. The GG genotype correlated with higher γ-IFN levels (P<0.05). In short, the OAS1 rs10774671 SNP GG genotype contributed to CA16 susceptibility and was associated with the development of mild HFMD.