The 863C>A and 1031T>C Single Nucleotide Polymorphisms (SNPs) in the Tumor Necrosis Factor Alpha (TNF-α) Promoter Gene May Not Be Putative Predictors of HBV Endemicity

Livers Pub Date : 2023-09-22 DOI:10.3390/livers3040037
Hussein Mukasa Kafeero, Dorothy Ndagire, Ponsiano Ocama, Charles Drago Kato, David Patrick Kateete, Abdul Walusansa, Ali Kudamba, Kigozi Edgar, Fred Ashaba Katabazi, Maria Magdalene Namaganda, Jamilu E. Ssenku, Eddie Wampande, Henry Kajumbula, Hakim Sendagire
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Abstract

Background: Genetic polymorphisms within the gene loci of the promoter region of tumor necrosis factor (TNF) alpha have been associated with the pathogenesis of hepatitis B virus (HBV) infection. In Uganda, there is a wide variation in the HBV endemicity, ranging from low endemicity, through moderate endemicity, to hyper-endemicity. However, the underlying reasons for this disparity in HBV burden are not fully elucidated. Thus, we aimed to test the hypothesis that the TNF-α-863C/A and -1031T/C polymorphic sites may have an effect on the difference between the burden of HBV in our country. We screened 384 participants, from which a sample of 134 was drawn, to determine the HBV, TNF-α-863C/A, and TNF-α-863T/C genotypes. The nucleotide BLAST was used to match the unknown targeted sequence obtained from the Sanger sequence against the known deposited sequence. This process unveiled the base substitution mutation and the HBV genotypes. The odds ratio (OR) and Chi-square test of proportions were used for the analysis. All the analyses were performed using SPSS version 26.0 and MedCalc software version 20.010 at 95% CI. A p < 0.05 was considered statistically significant. Results: The prevalence of both the TNF-α-863C/A and the TNF-α-1031T/C genotypes and their alleles did not differ significantly by endemicity (p > 0.05). However, the prevalence of the nucleotide substitution mutations for TNF-α-863C>A and TNF-α-1031T>C was significantly low for all the study groups (p < 0.05). Conclusion: The TNF-α gene promoter at the TNF-α-863C/A and 1031T/C positions is conserved in our population and may not affect the endemicity of HBV infection. However, future research should focus on the use of nationwide samples in order to reach concreate determinations regarding the role of the TNF-α polymorphisms in the risk/resolution of HBV infections in an African or Black population.
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肿瘤坏死因子α (TNF-α)启动子基因的863C>A和1031T>C单核苷酸多态性(SNPs)可能不是推测的HBV地方性的预测因子
背景:肿瘤坏死因子(TNF) α启动子区域基因位点的遗传多态性与乙型肝炎病毒(HBV)感染的发病机制有关。在乌干达,乙型肝炎病毒的地方性差异很大,从低地方性,到中等地方性,再到高地方性。然而,乙肝病毒负担差异的根本原因尚未完全阐明。因此,我们旨在验证TNF-α-863C/A和-1031T/C多态性位点可能影响我国HBV负担差异的假设。我们筛选了384名参与者,从中抽取了134名样本,以确定HBV, TNF-α-863C/ a和TNF-α-863T/C基因型。利用核苷酸BLAST将从Sanger序列中获得的未知目标序列与已知沉积序列进行比对。这一过程揭示了碱基置换突变和HBV基因型。采用比值比(OR)和卡方比例检验进行分析。所有分析均采用SPSS 26.0版和MedCalc 20.010版软件进行,95% CI。A & p;0.05认为有统计学意义。结果:TNF-α-863C/A和TNF-α-1031T/C基因型及其等位基因在不同地区的患病率差异无统计学意义(p >0.05)。然而,TNF-α-863C>A和TNF-α-1031T>C的核苷酸替代突变发生率在所有研究组中均明显较低(p <0.05)。结论:TNF-α基因启动子TNF-α- 863c /A和1031T/C位点在我国人群中具有保守性,可能不影响HBV感染的地方性。然而,未来的研究应该集中在全国范围内的样本的使用上,以获得关于TNF-α多态性在非洲或黑人人群中HBV感染风险/解决方案中的作用的具体确定。
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