Relationship between interleukin-37 genetic polymorphisms and HBV-related liver disease in a Chinese Han cohort

Hepatitis B virus (HBV)-related liver disease is an inflammatory-associated disease, with diverse clinical phenotypes ranging from asymptomatic HBV carriers to hepatocellular carcinoma. Interleukin-37 (IL-37), a cytokine that effectively inhibits innate and adaptive immunity, has powerful anti-inflammatory and anti-tumor effects. Several single nucleotide polymorphisms (SNPs) in the IL37 gene are genetic predictive risk factors for HBV infection and HBV-mediated liver disease progression. However, different ethnic groups may have different allele frequencies and linkage disequilibrium structures. The effect of SNPs in IL37 on HBV infection and its relationship with different clinical outcomes have not been clarified among the Han people in southern China. Based on in silico functional prediction and previously reported in the literature to be potentially associated with diseases, we screened seven potentially functional SNPs (rs3811046, rs3811047, rs2723176, rs2723186, rs4611652, rs4392270, and rs4241122) located in the IL37 genomic region and 3-kb upstream and downstream of the gene body. 1,582 subjects were included in the study, including 747 patients with HBV-related liver disease, 405 patients who cleared HBV, and 430 healthy controls. The seven SNPs were genotyped using the SNaPshot SNP assay, and co-dominant, dominant, and recessive models were used to explore the association of each SNP with HBV infection and clinical outcomes after HBV infection. The rs4241122 demonstrated a significant association with both HBV infection and its clinical outcomes, with the GG genotype identified as an independent protective factor for spontaneous clearance of HBV. The rs2723186 and rs4392270 were also significantly associated with HBV clearance under specific genetic models. Furthermore, rs3811046 and rs3811047 were correlated with the progression of liver abnormalities following HBV infection. Our data suggests that SNPs at the IL37 locus are associated with susceptibility to HBV infection and clinical outcomes after HBV infection.