Generic placeholder image

Current Cancer Therapy Reviews

Editor-in-Chief

ISSN (Print): 1573-3947
ISSN (Online): 1875-6301

Research Article

HLA-DQ Gene Polymorphisms Associated with Hepatitis B Virus in Patients with Hepatocellular Carcinoma Progression

Author(s): Amal A. Mohamed, Adel A.-H. Abdel-Rahman, Somia Saad, Shrook Mousa, Omnia Tantawi, Fawkia E. Zahran, Nevine F. Shafik, Reham A.A. Elshimy, Ayman A.-H. Alkhalegy, Alaa Kandil, Rehab Ahmed, Mahmoud Khalil, Moataz Y. Soliman, Yousry E.-E. Abo-Amer and Sherief Abd-Elsalam*

Volume 17, Issue 1, 2021

Published on: 12 July, 2020

Page: [75 - 81] Pages: 7

DOI: 10.2174/1573394716666200712151208

Price: $65

Abstract

Background: The development and progression of hepatitis B (HBV)-related disease can lead to liver cirrhosis and hepatocellular carcinoma (LC and HCC, respectively). Human leukocyte antigen (HLA) DQ polymorphism has been reported in other recent studies to deal with the association between HBV and liver disease. Our study on the Egyptian population was introduced to assess the strong association between HLA-DQ polymorphism and HBV infection in addition to the progression of HCC.

Aim: The aim of this work was to estimate HLA-DQ gene polymorphisms in HBV and HCC.

Methods: HLA-DQ genotype polymorphism was assayed by using the ABI Taq Man allelic discrimination assay in different groups in this study. According to the relevant HLA Class II single nucleotide polymorphism (SNP) literature, one single nucleotide polymorphism (SNPs) was selected as the candidate site; it was an HLA-DQ, which showed minor allele frequencies AA, GA, and GG.

Results: Haplotype analysis was performed on all the subjects in the study; AA haplotype was the most frequent haplotype in HCC cases (18%) in comparison with HBV and healthy individuals (3%). The haplotype GA was more frequent in the HCC group and slightly more frequent in LC when compared to HBV only cases and also when compared to the control group. In contrast, the GG haplotype was recorded less frequently in HCC individuals, but the HBV and LC groups showed more frequency of this haplotype compared with the HCC group. There was a correlation between AFP serum levels and the frequency of GA and AA polymorphism in HCC cases.

Conclusion: We found that AA and GA haplotype was significantly most frequent in HCC. Our findings suggest that HLA-DQ AA and GG polymorphism might serve as a novel potential predictive marker for HCC and may function in tumorigenesis of HBV.

Keywords: HLA-DQ, HBV, HCC, liver cirrhosis, gene-polymorphism, tumorigenesis.

Graphical Abstract

[1]
Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015. CA Cancer J Clin 2015; 65(1): 5-29.
[http://dx.doi.org/10.3322/caac.21254 ] [PMID: 25559415]
[2]
McGlynn KA, London WT. The global epidemiology of hepatocellular carcinoma: Present and future Clin Liver Dis 2011; 15(2): 223-\43.
[http://dx.doi.org/10.1016/j.cld.2011.03.006 ] [PMID: 21689610]
[3]
Yuen MF, Hou JL, Chutaputti A. Asia Pacific Working Party on Prevention of Hepatocellular Carcinoma. Hepatocellular carcinoma in the Asia pacific region. J Gastroenterol Hepatol 2009; 24(3): 346-53.
[http://dx.doi.org/10.1111/j.1440-1746.2009.05784.x ] [PMID: 19220670]
[4]
Lok AS. Does antiviral therapy for hepatitis B and C prevent hepatocellular carcinoma? J Gastroenterol Hepatol 2011; 26(2): 221-7.
[http://dx.doi.org/10.1111/j.1440-1746.2010.06576.x ] [PMID: 21070361]
[5]
Yao M, Wang L, Dong Z, et al. Glypican-3 as an emerging molecular target for hepatocellular carcinoma gene therapy. Tumour Biol 2014; 35(6): 5857-68.
[http://dx.doi.org/10.1007/s13277-014-1776-5 ] [PMID: 24633918]
[6]
Luo HC, Zhang HB, Xin XJ, Huang WX. Haplotype-based case- control study of DNA repair gene XRCC3 and hepatocellular carcinoma risk in a Chinese population. Tumour Biol 2014; 35(4): 3415-9.
[http://dx.doi.org/10.1007/s13277-013-1451-2 ] [PMID: 24307625]
[7]
Zheng YB, Huang JW, Zhan MX, et al. Genetic variants in the KDR gene is associated with the prognosis of transarterial chemoembolization treated hepatocellular carcinoma. Tumour Biol 2014; 35(11): 11473-81.
[http://dx.doi.org/10.1007/s13277-014-2478-8 ] [PMID: 25123269]
[8]
Lu Y, Wu Z, Peng Q, et al. Role of IL-4 gene polymorphisms in HBV-related hepatocellular carcinoma in a Chinese population. PLoS One 2014; 9(10): e110061.
[9]
Cheong JY, Cho SW, Choi JY, et al. RANTES, MCP-1, CCR2, CCR5, CXCR1 and CXCR4 gene polymorphisms are not associated with the outcome of hepatitis B virus infection: Results from a large scale single ethnic population. J Korean Med Sci 2007; 22(3): 529-35.
[http://dx.doi.org/10.3346/jkms.2007.22.3.529 ] [PMID: 17596666]
[10]
Godkin A, Davenport M, Hill AV. Molecular analysis of HLA class II associations with hepatitis B virus clearance and vaccine nonresponsiveness. Hepatology 2005; 41(6): 1383-90.
[http://dx.doi.org/10.1002/hep.20716 ] [PMID: 15915462]
[11]
Zhang X, Jia J, Dong J, et al. HLA-DQ polymorphisms with HBV infection: different outcomes upon infection and prognosis to lamivudine therapy. J Viral Hepat 2014; 21(7): 491-8.
[http://dx.doi.org/10.1111/jvh.12159 ] [PMID: 24750255]
[12]
Al-Qahtani AA, Al-Anazi MR, Abdo AA, et al. Association between HLA variations and chronic hepatitis B virus infection in Saudi Arabian patients PLoS One 2014; 9(1): e80445, 1.
[13]
Li S, Yang Y, Zhao W,, et al. Qian J, GWAS identifies novel susceptibility loci on 6p21.32 and 21q21.3 for hepatocellular carcinoma in chronic hepatitis B virus carriers. PLoS Genet 2012; 8(7): e1002791.
[14]
Wen J, Song C, Jiang D, et al. Hepatitis B virus genotype, mutations, human leukocyte antigen polymorphisms and their interactions in hepatocellular carcinoma: A multi-centre case-control study. Sci Rep 2015; 5(5): 16489-99.
[http://dx.doi.org/10.1038/srep16489 ] [PMID: 26568165]
[15]
Mbarek H, Ochi H, Urabe Y, et al. A genome-wide association study of chronic hepatitis B identified novel risk locus in a Japanese population. Hum Mol Genet 2011; 20(19): 3884-92.
[http://dx.doi.org/10.1093/hmg/ddr301 ] [PMID: 21750111]
[16]
Zhu AX. Molecularly targeted therapy for advanced hepatocellular carcinoma in 2012: Current status and future perspectives. Semin Oncol 2012; 39(4): 493-502.
[http://dx.doi.org/10.1053/j.seminoncol.2012.05.014 ] [PMID: 22846866]
[17]
Savas S, Shariff M, Taylor IW, Ozcelik H. Human non-synonymous single nucleotide polymorphisms can influence ubiquitin- mediated protein degradation. OMICS 2007; 11(2): 200-8.
[http://dx.doi.org/10.1089/omi.2007.4324 ] [PMID: 17594238]
[18]
Jiang L, Zhang C, Li Y, et al. A non-synonymous polymorphism Thr115Met in the EpCAM gene is associated with an increased risk of breast cancer in Chinese population. Breast Cancer Res Treat 2011; 126(2): 487-95.
[http://dx.doi.org/10.1007/s10549-010-1094-6 ] [PMID: 20683652]
[19]
Dakal TC, Kala D, Dhiman G, Yadav V, Krokhotin A, Dokholyan NV. Predicting the functional consequences of non-synonymous single nucleotide polymorphisms in IL8 gene. Sci Rep 2017; 7(1): 6525-33.
[http://dx.doi.org/10.1038/s41598-017-06575-4 ] [PMID: 28747718]
[20]
Huang W, Zhang H, Hao Y, et al. A non-synonymous single nucleotide polymorphism in the HJURP gene associated with susceptibility to hepatocellular carcinoma among Chinese. PLoS One 2016; 11(2): e0148618.
[http://dx.doi.org/10.1371/journal.pone.0148618 ] [PMID: 26863619]
[21]
Matsuura K, Isogawa M, Tanaka Y. Host genetic variants influencing the clinical course of hepatitis B virus infection. J Med Virol 2016; 88(3): 371-9.
[http://dx.doi.org/10.1002/jmv.24350 ] [PMID: 26255971]
[22]
Ji X, Zhang Q, Li B, et al. Impacts of human leukocyte antigen DQ genetic polymorphisms and their interactions with hepatitis B virus mutations on the risks of viral persistence, liver cirrhosis, and hepatocellular carcinoma. Infect Genet Evol 2014; 28: 201-9.
[http://dx.doi.org/10.1016/j.meegid.2014.09.032 ] [PMID: 25281206]
[23]
Trinks J, Nishida N, Hulaniuk ML, et al. Role of HLA-DP and HLA-DQ on the clearance of hepatitis B virus and the risk of chronic infection in a multiethnic population. Liver Int 2017; 37(10): 1476-87.
[http://dx.doi.org/10.1111/liv.13405 ] [PMID: 28267888]
[24]
Hu Z, Liu Y, Zhai X, et al. New loci associated with chronic hepatitis B virus infection in Han Chinese. Nat Genet 2013; 45(12): 1499-503.
[http://dx.doi.org/10.1038/ng.2809 ] [PMID: 24162738]
[25]
Xu T, Sun M, Wang H. Relationship between HLA-DQ gene polymorphism and hepatitis B virus infection. BioMed Res Int 2017; 2017: 9679843.
[http://dx.doi.org/10.1155/2017/9679843 ] [PMID: 28512640]
[26]
Liao Y, Cai B, Li Y, et al. Association of HLA-DP/DQ, STAT4 and IL-28B variants with HBV viral clearance in Tibetans and Uygurs in China. Liver Int 2015; 35(3): 886-96.
[http://dx.doi.org/10.1111/liv.12643 ] [PMID: 25041342]
[27]
Huang P, Fan H, Tian T, et al. The relationship between human leukocyte antigen-DP/DQ gene polymorphisms and the outcomes of HCV infection in a Chinese population. Virol J 2017; 14(1): 235-41.
[http://dx.doi.org/10.1186/s12985-017-0901-7 ] [PMID: 29212520]
[28]
Armitage P, Berry G, Matthews JNS. Statistical methods in medical research. Blackwell Science Ltd.: UK, 2002.

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy