Association of IL-13 , S100B , and TLR-7 Gene Polymorphisms with Enterovirus 71 Infection in Hand, Foot, and Mouth Disease in China

AIM: This study was conducted to determine if single nucleotide polymorphisms within the interleukin (IL)-13 (rs20541 locus), the S100B (rs9722 locus), and the toll-like receptor (TLR)-7 (rs179019 and rs3853839 loci) genes are associated with the clinical severity of disease caused by enterovirus 71 (EV71) in children suffering from hand, foot, and mouth disease (HFMD). MATERIALS AND METHODS: A total of 355 children, diagnosed with HFMD, were divided into two groups: severe (totaling 162 cases) and mild (totaling 193 cases). Three hundred healthy children were recruited as a control group. The gene polymorphisms of the rs20541 locus in the IL-13 gene; the rs9722 locus in the S100B gene; and the rs179019 and the rs3853839 loci in the TLR-7 gene were analyzed with Sanger sequencing. The expression levels of IL-13, S100B, interferon (IFN)-α, IL-6 and the relative expression level of TLR-7 were calculated for each genotype. RESULTS: This study demonstrated that the T allele at the rs9722 locus of the S100B gene was a significant risk factor for severe HFMD. The rs3853839 C allele of the TLR-7 gene was also a risk factor for severe HFMD in both male and female patients. The G allele at the rs20541 locus of IL-13 gene and the A allele at the rs179019 locus of the TLR-7 gene were not risk factors for severe HFMD in either male or female patients. CONCLUSION: The T allele at the rs9722 locus of S100B gene is a risk factor for the severe HFMD caused by EV71 infection, of which the mechanism may be due to the promotion of S100B protein secretion. The allele C at TLR-7 rs3853839 locus is a risk factor for the severe HFMD caused by EV71 infection, which may be related to a reduction of the relative expression of TLR-7, IFN-α, and IL-6.