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  • Title: Genetic variants in class II transactivator are associated with chronic hepatitis B virus infection in the Han Chinese population.
    Author: Su M, Chen Z, Zheng J, Chen Y.
    Journal: Int J Immunogenet; 2020 Oct; 47(5):435-442. PubMed ID: 32103629.
    Abstract:
    Class II transactivator (CIITA) is a master regulator of MHC gene expression and plays a role in inducing the expression of other immune system genes, including IL-4, IL-10 and Fas ligand, as well as more than 60 other immunologically significant genes. We used CIITA as a candidate gene to analyse whether any single-nucleotide polymorphisms (SNPs) are associated with chronic hepatitis B virus (HBV) infection. In total, 773 patients with chronic HBV infection were enrolled in this hospital-based case-control study. The patients were divided into groups according to their clinical characteristics: 596 patients had chronic hepatitis B (CHB), and 177 patients had hepatocellular carcinoma (HCC). A total of 313 patients with self-limited HBV infection were selected as the control group. CIITA gene variants were screened using Haploview 4.2 software; improved multiplex ligation detection reaction technology was then used for genotype detection, and HaploReg v4.1 was employed to predict the functions of 15 variants. The results showed that SNPs in introns in the CIITA gene, namely, rs13333382 (TT + TA vs. AA: p = .003, odds ratio (OR) = 0.65, 95% confidence interval (CI) = 0.49-0.87) and rs4780335 (CC + CG vs. GG: p = 9.40 × 10-5 , OR = 0.55, 95% CI = 0.41-0.74), were positively associated with self-limited HBV infection in the dominant genetic model. Additionally, SNP rs1139564 (TT + TC vs. CC: p = .002, OR = 1.61, 95% CI = 1.19-2.16) in the 3' untranslated region may increase the risk of CHB. According to in silico analysis, all three statistically significant variants act as transcription factor binding motifs. However, we did not find that these 15 mutations are associated with HCC risk. Therefore, we believe that CIITA is a susceptibility gene for CHB rather than for HCC.
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