Genetic variants in IL33 and IL1RL1 genes confer susceptibility to HBV-related liver cirrhosis in Chinese Han population

Ning Ma; Mengyuan Xu; Yi Dong; Fengxue Yu; Xiaolin Zhang; Xia Gao; Yanxin Meng; Ping Gao; Jin Zhou; Meina Yuan; Yingjun Mi; Sufen Qi; Lu Li; Dianwu Liu; Wenxuan Liu; Lei Yang

doi:10.1016/j.meegid.2021.104983

Genetic variants in IL33 and IL1RL1 genes confer susceptibility to HBV-related liver cirrhosis in Chinese Han population

Infect Genet Evol. 2021 Oct:94:104983. doi: 10.1016/j.meegid.2021.104983. Epub 2021 Jun 29.

Authors

Ning Ma¹, Mengyuan Xu², Yi Dong³, Fengxue Yu⁴, Xiaolin Zhang², Xia Gao², Yanxin Meng⁵, Ping Gao¹, Jin Zhou¹, Meina Yuan¹, Yingjun Mi¹, Sufen Qi¹, Lu Li¹, Dianwu Liu², Wenxuan Liu⁶, Lei Yang⁷

Affiliations

¹ Department of Social Medicine and Health Care Management, School of Public Health, Hebei Medical University, Hebei Key Laboratory of Environment and Human Health, Shijiazhuang 050017, China.
² Department of Epidemiology and Statistics, School of Public Health, Hebei Medical University, Hebei Key Laboratory of Environment and Human Health, Shijiazhuang 050017, China.
³ Department of School of Basic Medical Sciences, Hebei Medical University, Shijiazhuang 050017, China.
⁴ Division of gastroenterology, The Second Hospital of Hebei Medical University, The Hebei Key Laboratory of Gastroenterology, Shijiazhuang 050017, China.
⁵ Antenatal diagnosis center, The fourth hospital of Shijiazhuang, Shijiazhuang 050017, China.
⁶ Department of Epidemiology and Statistics, School of Public Health, Hebei Medical University, Hebei Key Laboratory of Environment and Human Health, Shijiazhuang 050017, China. Electronic address: wenxuanl10@163.com.
⁷ Department of Epidemiology and Statistics, School of Public Health, Hebei Medical University, Hebei Key Laboratory of Environment and Human Health, Shijiazhuang 050017, China. Electronic address: leileiy10@126.com.

PMID: 34197916
DOI: 10.1016/j.meegid.2021.104983

Abstract

Introduction: Previous studies indicate that the IL-33/ST2 pathway is involved in hepatitis B virus (HBV) -related liver diseases. This study aimed to determine the relationship between genetic variants in IL-33/ST2 pathway with susceptibility to liver cirrhosis.

Materials and methods: A total of 2632 Han Chinese samples met the inclusion and exclusion criteria, including 840 negative controls (NeC), 691 chronic hepatitis B (CHB), 680 HBV-related liver cirrhosis (LC) and 421 HBV-related hepatocellular carcinoma (HCC) (without LC) patients. Four polymorphisms (IL33-rs4742170, rs1048274, rs10975519 and IL1RL1-rs1041973) were selected and genotyping was performed. All statistical analyses were performed by SPSS21.0, mainly using the Hardy-Weinberg equilibrium test, Pearson chi-square, unconditional Logistic regression and haplotype analysis.

Results: After adjusting for age, sex, smoking and drinking, significant associations were observed between IL33-rs4742170, rs1048274 and rs10975519 polymorphisms with LC risk. NeC with IL33-rs4742170 CC genotype was 1.80 times more likely to develop LC compared with TT genotype, while NeC with rs10975519(TC + CC) genotype was 1.32 times more likely to develop LC when compared with the TT genotype. CHB cases with rs4742170(CC + TC) genotype had 1.30 times higher susceptibility to develop LC compared with the TT genotype. The IL33-rs1048274G allele occurred more frequently in the LC group compared with the HCC group in codominant model (AG/AA: P = 0.001, OR = 1.66, 95%CI = 1.22-2.25; GG/AA: P = 0.018, OR = 1.54, 95%CI = 1.08-2.20). The IL33 haplotype CG conformed by rs10975519C and rs1048274G was more frequent in the LC group than in the NeC group and CHB group. Moreover, the IL33 haplotype CCG conformed by rs4742170C, rs10975519C and rs1048274G was found to be more frequent in the LC group than the HCC group. However, there was no association between IL1RL1-rs1041973 and LC risk.

Conclusion: Our findings demonstrate the association between genetic variants in IL33 with susceptibility to liver cirrhosis. IL33-rs4742170C, rs1048274G and rs10975519C could serve as biomarkers of LC.

Keywords: HBV; IL1RL1; IL33; Liver cirrhosis; Polymorphism.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Aged
China
Female
Genetic Predisposition to Disease / genetics*
Hepatitis B / genetics*
Hepatitis B / virology
Hepatitis B virus / physiology*
Hepatitis B, Chronic / genetics
Hepatitis B, Chronic / virology
Humans
Interleukin-1 Receptor-Like 1 Protein / genetics*
Interleukin-1 Receptor-Like 1 Protein / metabolism
Interleukin-33 / genetics*
Interleukin-33 / metabolism
Liver Cirrhosis / genetics*
Liver Cirrhosis / virology
Male
Middle Aged
Polymorphism, Single Nucleotide*

Substances

IL1RL1 protein, human
IL33 protein, human
Interleukin-1 Receptor-Like 1 Protein
Interleukin-33