Comprehensive Investigating of Mismatch Repair Genes (MMR) Polymorphisms in Participants with Chronic Hepatitis B Virus Infection

Overview

Journal Front Genet

Date 2023 Feb 23

PMID 36816025

Authors

Ning Ma

Yucheng Sun

Yanan Kong

Yiyao Jin

Fengxue Yu

Lianfeng Liu

Lei Yang

Wenxuan Liu

Xia Gao

Dianwu Liu

Xiaolin Zhang

Lu Li

Affiliations

Soon will be listed here.

Abstract

In this study, we focused on the relationship between single nucleotide polymorphisms in MMR genes and the occurrence and development of HBV infection. A total of 3,128 participants were divided into five groups: negative control group (NeC), spontaneous clearance group (SC), chronic hepatitis B group (CHB), liver cirrhosis group (LC) and hepatocellular carcinoma group (HCC), CHB, liver cirrhosis and hepatocellular carcinoma constitute HLD. We conducted three case-control studies: NeC (840 cases) vs. HLD (1792 cases), SC (486 cases) vs. HLD (1792 cases) and CHB + LC (1,371 cases) vs. HCC (421 cases). 11 polymorphic loci in and were involved in genotyping by Sequenom MassArray. The SNPStats performed Hardy-Weinberg equilibrium test. Linkage disequilibrium patterns were visualized using Haploview4.2. The GMDR (v0.9) was conducted to generalized multifactor dimension reduction analysis. The correlation, multiplicative interaction and additive interaction analyses were calculated by Logistic Regression through SPSS21.0. Matrix and programmed excel were also involved in the calculation of additive interaction. In NeC vs. HLD group, -rs1150793(G) was a risk base to HBV susceptibility (nominal = 0.002, OR = 1.346). We found multiplicative interaction between -rs1540354 (AA + AT) and -rs1233255 (AA) (nominal = 0.024, OR = 1.240). There was additive interaction between -rs1233255 (AA) and -rs256554(CA + CC). In SC vs. HLD group, -rs1540354 (TT) was a risk genotype (nominal < 0.05, OR>1). Through haplotype analysis, we found the linkage disequilibrium of three loci in . The results of GMDR showed the optimal five-locus model about the spontaneous clearance of HBV. In CHB + LC vs. HCC group, -rs12112229(A) was related to the cancerization of liver. We found rs1150793(G), rs1540354(T) and rs12112229(A) were significantly related to HBV susceptibility, spontaneous clearance of HBV and cancerization after infection, respectively.

References

Terrault N, Bzowej N, Chang K, Hwang J, Jonas M, Murad M . AASLD guidelines for treatment of chronic hepatitis B. Hepatology. 2015; 63(1):261-83. PMC: 5987259. DOI: 10.1002/hep.28156. View

Guan J, Lu C, Jin Q, Lu H, Chen X, Tian L . MLH1 Deficiency-Triggered DNA Hyperexcision by Exonuclease 1 Activates the cGAS-STING Pathway. Cancer Cell. 2020; 39(1):109-121.e5. PMC: 8666006. DOI: 10.1016/j.ccell.2020.11.004. View

Liu N, Zhang K, Zhao H . Haplotype-association analysis. Adv Genet. 2008; 60:335-405. DOI: 10.1016/S0065-2660(07)00414-2. View

Fujikura K, Akita M, Ajiki T, Fukumoto T, Itoh T, Zen Y . Recurrent Mutations in APC and CTNNB1 and Activated Wnt/β-catenin Signaling in Intraductal Papillary Neoplasms of the Bile Duct: A Whole Exome Sequencing Study. Am J Surg Pathol. 2018; 42(12):1674-1685. DOI: 10.1097/PAS.0000000000001155. View

Liu Y, Zhang X, Jia J, Tang L, Gao X, Yan L . Correlation between polymorphisms in DNA mismatch repair genes and the risk of primary hepatocellular carcinoma for the Han population in northern China. Scand J Gastroenterol. 2015; 50(11):1404-10. DOI: 10.3109/00365521.2015.1045429. View

Si J, Yu C, Guo Y, Bian Z, Meng R, Yang L . Chronic hepatitis B virus infection and total and cause-specific mortality: a prospective cohort study of 0.5 million people. BMJ Open. 2019; 9(4):e027696. PMC: 6500223. DOI: 10.1136/bmjopen-2018-027696. View

Shamloo B, Usluer S . p21 in Cancer Research. Cancers (Basel). 2019; 11(8). PMC: 6721478. DOI: 10.3390/cancers11081178. View

Vollmers S, Lobermeyer A, Niehrs A, Fittje P, Indenbirken D, Nakel J . Host KIR/HLA-C Genotypes Determine HIV-Mediated Changes of the NK Cell Repertoire and Are Associated With Vpu Sequence Variations Impacting Downmodulation of HLA-C. Front Immunol. 2022; 13:922252. PMC: 9334850. DOI: 10.3389/fimmu.2022.922252. View

Chen P, Dudley S, Hagen W, Dizon D, Paxton L, Reichow D . Contributions by MutL homologues Mlh3 and Pms2 to DNA mismatch repair and tumor suppression in the mouse. Cancer Res. 2005; 65(19):8662-70. DOI: 10.1158/0008-5472.CAN-05-0742. View

10.

Suppiah V, Moldovan M, Ahlenstiel G, Berg T, Weltman M, Abate M . IL28B is associated with response to chronic hepatitis C interferon-alpha and ribavirin therapy. Nat Genet. 2009; 41(10):1100-4. DOI: 10.1038/ng.447. View

11.

Yim H, Lok A . Natural history of chronic hepatitis B virus infection: what we knew in 1981 and what we know in 2005. Hepatology. 2006; 43(2 Suppl 1):S173-81. DOI: 10.1002/hep.20956. View

12.

Chong I, Cunningham D, Barber L, Campbell J, Chen L, Kozarewa I . The genomic landscape of oesophagogastric junctional adenocarcinoma. J Pathol. 2013; 231(3):301-10. DOI: 10.1002/path.4247. View

13.

Wang G, Li J, Yao Y, Liu Y, Xia P, Zhang H . Small nucleolar RNA 42 promotes the growth of hepatocellular carcinoma through the p53 signaling pathway. Cell Death Discov. 2021; 7(1):347. PMC: 8581050. DOI: 10.1038/s41420-021-00740-5. View

14.

Zhang H, Fu L . The role of ALDH2 in tumorigenesis and tumor progression: Targeting ALDH2 as a potential cancer treatment. Acta Pharm Sin B. 2021; 11(6):1400-1411. PMC: 8245805. DOI: 10.1016/j.apsb.2021.02.008. View

15.

Zhu X, Liu W, Qiu X, Wang Z, Tan C, Bei C . Single nucleotide polymorphisms in predict poor prognosis of hepatocellular carcinoma in a Chinese population. Oncotarget. 2017; 8(45):80039-80049. PMC: 5668119. DOI: 10.18632/oncotarget.16899. View

16.

Apps R, Del Prete G, Chatterjee P, Lara A, Brumme Z, Brockman M . HIV-1 Vpu Mediates HLA-C Downregulation. Cell Host Microbe. 2016; 19(5):686-95. PMC: 4904791. DOI: 10.1016/j.chom.2016.04.005. View

17.

Wang X, Singh P, Zhou L, Sharafeldin N, Landier W, Hageman L . Genome-Wide Association Study Identifies as a Novel Susceptibility Gene for Anthracycline-Related Cardiomyopathy in Childhood Cancer Survivors. J Clin Oncol. 2022; 41(9):1758-1769. PMC: 10043563. DOI: 10.1200/JCO.22.01527. View

18.

Langeberg W, Kwon E, Koopmeiners J, Ostrander E, Stanford J . Population-based study of the association of variants in mismatch repair genes with prostate cancer risk and outcomes. Cancer Epidemiol Biomarkers Prev. 2010; 19(1):258-64. PMC: 2825566. DOI: 10.1158/1055-9965.EPI-09-0800. View

19.

Meder B, Ruhle F, Weis T, Homuth G, Keller A, Franke J . A genome-wide association study identifies 6p21 as novel risk locus for dilated cardiomyopathy. Eur Heart J. 2013; 35(16):1069-77. DOI: 10.1093/eurheartj/eht251. View

20.

Desalegn H, Aberra H, Berhe N, Medhin G, Mekasha B, Gundersen S . Predictors of mortality in patients under treatment for chronic hepatitis B in Ethiopia: a prospective cohort study. BMC Gastroenterol. 2019; 19(1):74. PMC: 6521482. DOI: 10.1186/s12876-019-0993-1. View