Interleukin‐21 receptor gene polymorphism is associated with hepatitis B virus‐related hepatocellular carcinoma in Chinese patients

BACKGROUND: We investigated the relationship between hepatitis B virus (HBV)‐related pathogenesis and single nucleotide polymorphisms (SNPs) in interleukin‐21 (IL‐21)‐JAK‐STAT signaling pathway genes. METHODS: We used the high‐resolution melting (HRM) method to genotype five SNPs (IL‐21 rs2221903, IL‐21 rs4833837, IL‐21 receptor (IL‐21R) rs2285452, JAK3 rs3008, and STAT3 rs1053023) in 546 HBV‐infected patients and 353 healthy Chinese subjects. The HBV‐infected patients were further divided into subgroups based on the HBV‐related pathologies: chronic hepatitis B (CHB), HBV‐related liver cirrhosis (LC), and HBV‐related hepatocellular carcinoma (HCC). RESULTS: There were no significant differences in the genotype and allele distributions of the five SNPs between the HBV‐infected patients and healthy subjects. The genotype and allele frequencies were similar in the two groups for IL‐21 rs2221903 (A>G, P = 0.83 and 0.67), rs4833837 (A>G, P = 0.80 and 0.49), IL‐21R rs2285452 (G>A, P = 0.25 and 0.68), STAT3 rs1053023 (A>G, P = 1.00 and 0.96), and JAK3 rs3008 (C>T, P = 0.32 and 0.54). However, patients with the IL‐21R rs2285452 AA genotype were more susceptible to HBV‐related HCC than those with the IL‐21R rs2285452 GA/GG genotype (P = 0.03, OR = 3.27, 95% CI = 1.16‐9.20). The serological marker model of “HBsAg+, HBeAg+, HBcAb+” was predominant among patients with HBV infection. However, there was no association between the genotype's distribution of the five SNPs and the serological marker models (P > 0.05). CONCLUSIONS: These findings demonstrate that the IL‐21R rs2285452 AA genotype increases the risk of HBV‐related HCC in Chinese patients.