Correlation between interleukin‑23 receptor gene polymorphisms and risk of hepatitis B virus infection in patients

Peng,Qiliu; Qin,Yanping; Chen,Zhiping; Deng,Yan; Xu,Juanjuan; Li,Shan; Qin,Xue

doi:10.3892/mmr.2013.1558

Correlation between interleukin‑23 receptor gene polymorphisms and risk of hepatitis B virus infection in patients

Authors:
- Qiliu Peng
- Yanping Qin
- Zhiping Chen
- Yan Deng
- Juanjuan Xu
- Shan Li
- Xue Qin
View Affiliations

Affiliations: Department of Clinical Laboratory, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China, Department of Occupational Health and Environmental Health, School of Public Health at Guangxi Medical University, Nanning, Guangxi 530021, P.R. China
Published online on: June 26, 2013 https://doi.org/10.3892/mmr.2013.1558
Pages: 613-620

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

There is an increasing amount of evidence supporting the hypothesis that the pathological stage from hepatitis to hepatocellular carcinoma (HCC) is a chronic inflammatory process. Interleukin‑23 (IL‑23) is an important mediator and modulator of inflammation. Specific polymorphisms in the genes encoding subunits of the IL‑23 receptor (IL‑23R) have been consistently observed to be associated with chronic immune‑mediated diseases. In the current study, these variants were hypothesized to affect the risk of hepatitis B virus infection in patients. Three polymorphisms in the IL‑23R gene (rs10889677, rs1884444 and rs11465817) were examined in 84 cases of chronic hepatitis B (HBV), 67 cases of HBV‑related liver cirrhosis, 89 cases of HBV‑related HCC and 94 healthy controls using the polymerase chain reaction (PCR)‑restriction fragment length polymorphism method and DNA sequencing. The results revealed that subjects with the TG genotype of rs1884444 appeared to have higher susceptibility to HCC compared with the TT genotype (adjusted odds ratio (OR), 2.86; 95% confidence interval (CI), 1.39‑5.85; P=0.00). The rs1884444 G allele was associated with a significantly increased risk of HCC compared with the T allele (adjusted OR, 1.58; 95% CI, 0.96‑2.60; P=0.07). The rs11465817 and rs10889677 polymorphisms of the IL‑23R gene were not observed as being relevant to liver disease. These observations indicate that the genetic variants in the IL‑23R gene may contribute to HCC development. Additional studies with larger sample sizes must be conducted to confirm the current observations.

View Figures

View References

1	Wang JS, Huang T, Su J, et al: Hepatocellular carcinoma and aflatoxin exposure in Zhuqing Village, Fusui County, People’s Republic of China. Cancer Epidemiol Biomarkers Prev. 10:143–146. 2001.PubMed/NCBI
2	Yeh FS, Yu MC, Mo CC, Luo S, Tong MJ and Henderson BE: Hepatitis B virus, aflatoxins and hepatocellular carcinoma in southern Guangxi, China. Cancer Res. 49:2506–2509. 1989.PubMed/NCBI
3	Tao P, Zhi-Ming L, Tang-Wei L, et al: Associated factors in modulating aflatoxin B1-albumin adduct level in three Chinese populations. Dig Dis Sci. 50:525–532. 2005. View Article : Google Scholar : PubMed/NCBI
4	Zemel R, Issachar A and Tur-Kaspa R: The role of oncogenic viruses in the pathogenesis of hepatocellular carcinoma. Clin Liver Dis. 15:261–279. 2011. View Article : Google Scholar : PubMed/NCBI
5	Oppmann B, Lesley R, Blom B, et al: Novel p19 protein engages IL-12p40 to form a cytokine, IL-23, with biological activities similar as well as distinct from IL-12. Immunity. 13:715–725. 2000. View Article : Google Scholar : PubMed/NCBI
6	Abraham C and Cho J: Interleukin-23/Th17 pathways and inflammatory bowel disease. Inflamm Bowel Dis. 15:1090–1100. 2009. View Article : Google Scholar : PubMed/NCBI
7	Jiang Z, Yang P, Hou S, et al: IL-23R gene confers susceptibility to Behcet’s disease in a Chinese Han population. Ann Rheum Dis. 69:1325–1328. 2010.PubMed/NCBI
8	Duerr RH, Taylor KD, Brant SR, et al: A genome-wide association study identifies IL-23R as an inflammatory bowel disease gene. Science. 314:1461–1463. 2006. View Article : Google Scholar : PubMed/NCBI
9	Venegas M, Beltrán CJ, Alvarez L, et al: IL-23R Arg381Gln polymorphism in Chilean patients with inflammatory bowel disease. Eur Cytokine Netw. 19:190–195. 2008.PubMed/NCBI
10	Wu Y, Lu Z, Chen Y, Xue F, Chen X and Zheng J: Replication of association between interleukin-23 receptor (IL-23R) and its ligand (IL-12B) polymorphisms and psoriasis in the Chinese Han population. Hum Immunol. 71:1255–1258. 2010. View Article : Google Scholar : PubMed/NCBI
11	Illes Z, Safrany E, Peterfalvi A, et al: 3′UTR C2370A allele of the IL-23 receptor gene is associated with relapsing-remitting multiple sclerosis. Neurosci Lett. 431:36–38. 2008.
12	Chen J, Lu Y, Zhang H, et al: A nonsynonymous polymorphism in IL23R gene is associated with risk of gastric cancer in a Chinese population. Mol Carcinog. 49:862–868. 2010. View Article : Google Scholar : PubMed/NCBI
13	Chen B, Zeng Z, Xu L, et al: IL23R +2199A/C polymorphism is associated with decreased risk of certain subtypes of gastric cancer in Chinese: a case-control study. Cancer Epidemiol. 35:165–169. 2011.
14	Chu H, Cao W, Chen W, et al: Potentially functional polymorphisms in IL-23 receptor and risk of esophageal cancer in a Chinese population. Int J Cancer. 130:1093–1097. 2012. View Article : Google Scholar : PubMed/NCBI
15	Poole EM, Curtin K, Hsu L, et al: Genetic variability in IL23R and risk of colorectal adenoma and colorectal cancer. Cancer Epidemiol. 36:e104–e110. 2012. View Article : Google Scholar : PubMed/NCBI
16	Chien MH, Hsin CH, Chou LS, et al: Interleukin-23 receptor polymorphism as a risk factor for oral cancer susceptibility. Head Neck. 34:551–556. 2012. View Article : Google Scholar : PubMed/NCBI
17	Martin M and Herceg Z: From hepatitis to hepatocellular carcinoma: a proposed model for cross-talk between inflammation and epigenetic mechanisms. Genome Med. 4:82012. View Article : Google Scholar : PubMed/NCBI
18	Shi YY and He L: SHEsis, a powerful software platform for analyses of linkage disequilibrium, haplotype construction and genetic association at polymorphism loci. Cell Res. 15:97–98. 2005. View Article : Google Scholar : PubMed/NCBI
19	Stephens M, Smith NJ and Donnelly P: A new statistical method for haplotype reconstruction from population data. Am J Hum Genet. 68:978–989. 2001. View Article : Google Scholar : PubMed/NCBI
20	Ban Y, Tozaki T, Taniyama M, Nakano Y, Yoneyama K, Ban Y and Hirano T: Association studies of the IL-23R gene in autoimmune thyroid disease in the Japanese population. Autoimmunity. 42:126–130. 2009. View Article : Google Scholar : PubMed/NCBI
21	Kim ES, Kim SW, Moon CM, et al: Interactions between IL17A, IL23R and STAT4 polymorphisms confer susceptibility to intestinal Behcet’s disease in Korean population. Life Sci. 90:740–746. 2012.PubMed/NCBI
22	Faragó B, Magyari L, Sáfrány E, et al: Functional variants of interleukin-23 receptor gene confer risk for rheumatoid arthritis but not for systemic sclerosis. Ann Rheum Dis. 67:248–250. 2008.PubMed/NCBI
23	Ferguson LR, Han DY, Fraser AG, Huebner C, Lam WJ and Morgan AR: IL23R and IL12B SNPs and haplotypes strongly associate with Crohn’s disease risk in a New Zealand population. Gastroenterol Res Pract. 2010:5394612010.PubMed/NCBI
24	Liao R, Sun TW, Yi Y, et al: Expression of TREM-1 in hepatic stellate cells and prognostic value in hepatitis B-related hepatocellular carcinoma. Cancer Sci. 103:984–992. 2012. View Article : Google Scholar : PubMed/NCBI
25	Szabo G and Lippai D: Molecular hepatic carcinogenesis: impact of inflammation. Dig Dis. 30:243–248. 2012. View Article : Google Scholar : PubMed/NCBI
26	Qin LX: Inflammatory immune responses in tumor microenvironment and metastasis of hepatocellular carcinoma. Cancer Microenviron. 5:203–209. 2012. View Article : Google Scholar : PubMed/NCBI
27	McGeachy MJ, Chen Y, Tato CM, et al: The interleukin 23 receptor is essential for the terminal differentiation of interleukin 17-producing effector T helper cells in vivo. Nat Immunol. 10:314–324. 2009. View Article : Google Scholar : PubMed/NCBI
28	Langowski JL, Zhang X, Wu L, et al: IL-23 promotes tumour incidence and growth. Nature. 442:461–465. 2006. View Article : Google Scholar : PubMed/NCBI
29	Zhang Z, Zhou B, Zhang J, et al: Association of interleukin-23 receptor gene polymorphisms with risk of ovarian cancer. Cancer Genet Cytogenet. 196:146–152. 2010. View Article : Google Scholar : PubMed/NCBI
30	Mancini G, Kan SH and Gallagher G: A novel insertion variant of the human IL-23 receptor-alpha chain transcript. Genes Immun. 9:566–569. 2008. View Article : Google Scholar : PubMed/NCBI
31	Seng KC and Seng CK: The success of the genome-wide association approach: a brief story of a long struggle. Eur J Hum Genet. 16:554–564. 2008. View Article : Google Scholar : PubMed/NCBI