Association of IL1RN VNTR and NKG2A polymorphisms with hepatitis E infection, a case study from western India

Abstract

Interleukin 1 receptor antagonist (IL1RN) is a competitive inhibitor of interleukin 1 (IL-1). Natural killer cells (NK cells) contribute to the elimination of viruses by their antiviral effector function, which depends on a balance between inhibitory and activating receptor genes such as NKG2D and NKG2A. Using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) assays, the association of intronic single-nucleotide polymorphisms (SNPs) in these genes with viral infection were assessed in 111 patients with hepatitis E virus (HEV) infection and 222 HEV-naive healthy controls. An SNP in the IL1RN (VNTR) gene revealed allele 2 to be associated with protection against HEV infection (IL1RN *1/*1 vs. IL1RN *2/*2, OR = 0.26, 95% CI = 0.14–0.47, p < 0.001). Similarly, a polymorphism in the intronic region of NKG2A revealed an association with protection in a co-dominant model (A/A vs. A/G: OR = 0.40; 95% CI = 0.24–0.67; A/A vs. G/G: OR = 0.25; 95% CI = 0.10–0.57; p < 0.05) and an association with susceptibility in a dominant model (A/A + A/G vs. G/G: OR = 2.28; 95% CI = 1.06–4.93; p < 0.05) and a recessive model (AA vs. AG + GG: OR = 2.71; 95% CI = 1.66–4.48; p < 0.001). Our data suggest that genetic polymorphisms in host NKG2A and IL1RN have both protective and detrimental roles in HEV infection, although their impact on disease outcome remains unknown.