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. 2019 Jun;33(5):e22860.
doi: 10.1002/jcla.22860. Epub 2019 Feb 13.

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

Tangyuheng Liu  1 , Jiajia Song  1 , Mei Zhang  1 , Siyue Li  1 , Jinya Zhang  1 , Xuejiao Hu  1 , Zhenzhen Zhao  1 , Wu Peng  1 , Qian Wu  1 , Hao Bai  1 , Yinyu Li  2 , Xiaojun Lu  1 , Binwu Ying  1
Affiliations

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

Tangyuheng Liu et al. J Clin Lab Anal. 2019 Jun.

Abstract

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.

Keywords: IL-21; IL-21R; JAK/STAT; hepatitis B virus; hepatocellular carcinoma; single nucleotide polymorphism.

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