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亚甲基四氢叶酸还原酶基因 C677T 和 A1298C 多态性作为乙型肝炎病毒感染的危险因素。

Impact of methylene-tetrahydrofolate reductase gene C677T and A1298C polymorphisms as a risk factor for hepatitis B virus infection.

机构信息

Departments of Medical Biology, Faculty of Medicine, Tokat Gaziosmanpasa University, Tokat, Türkiye.

Department of Genetics, Faculty of Veterinary Medicine of Ondokuz Mayis University, Samsun, Türkiye.

出版信息

Nucleosides Nucleotides Nucleic Acids. 2023;42(9):683-695. doi: 10.1080/15257770.2023.2187061. Epub 2023 Mar 15.

Abstract

Chronic hepatitis B infection caused by Hepatitis B virus (HBV), influences over two billion people worldwide despite having an effective vaccine. With a total prevalence of 4.57%, there are 3.3 million estimated HBV carriers in Türkiye. Methylene-tetrahydrofolate reductase (MTHFR) arrange folate metabolism through nucleic acid synthesis and DNA methylation. C677T (rs1801133, p.Ala222Val) and A1298C (rs1801131, p.Glu429Ala) polymorphisms of gene have effect of reducing the activity of enzyme. We purposed to investigate the correlation between C677T and A1298C polymorphisms of gene with HBV infection in a Turkish population. One hundred eighteen HBV-infected participants and ninety healthy controls were incorporated in this research. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay was applied to discover the genotypes of polymorphisms. We demonstrated that T allele and CT + TT genotype frequencies of C677T polymorphism were significantly increased in HBV-infected participants than healthy controls [ = 0.015, OR (95% Cl) = 1.7 (1.11-2.79) and  = 0.020, OR (95% Cl) = 1.9 (1.10-3.42), respectively). No significant associations were noted concerning the A1298C polymorphism ( > 0.05). CC-AA composite genotype was observed to be significantly elevated in healthy controls than HBV-infected participants (32.2% vs. 13.6%,  = 0.001). In addition, the frequency of T-C haplotype was found to be considerably higher in the patient group than control group (15.8% vs 11.8%,  = 0.018). In conclusion, we found that T allele of C677T polymorphism poses a risk factor for HBV infection. We also discovered a protective impact of the CC-AA composite genotype against HBV infection and a risk effect of the T-A haplotype for HBV-infection.

摘要

乙型肝炎病毒(HBV)引起的慢性乙型肝炎感染影响着全球超过 20 亿人,尽管有有效的疫苗。在土耳其,总流行率为 4.57%,估计有 330 万 HBV 携带者。亚甲基四氢叶酸还原酶(MTHFR)通过核酸合成和 DNA 甲基化来调节叶酸代谢。基因的 C677T(rs1801133,p.Ala222Val)和 A1298C(rs1801131,p.Glu429Ala)多态性降低了酶的活性。我们旨在研究土耳其人群中基因 C677T 和 A1298C 多态性与 HBV 感染之间的相关性。本研究纳入了 118 名 HBV 感染患者和 90 名健康对照者。应用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)分析检测基因多态性的基因型。我们发现,与健康对照组相比,HBV 感染患者的 C677T 多态性 T 等位基因和 CT+TT 基因型频率显著升高[=0.015,OR(95%Cl)=1.7(1.11-2.79)和=0.020,OR(95%Cl)=1.9(1.10-3.42)]。A1298C 多态性无显著相关性(>0.05)。与 HBV 感染患者相比,健康对照组的 CC-AA 复合基因型显著升高(32.2%比 13.6%,=0.001)。此外,与对照组相比,患者组 T-C 单倍型频率明显较高(15.8%比 11.8%,=0.018)。总之,我们发现 C677T 多态性的 T 等位基因是 HBV 感染的危险因素。我们还发现 CC-AA 复合基因型对 HBV 感染有保护作用,T-A 单倍型对 HBV 感染有风险作用。

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