Department of Medical Biochemistry, Medical University of Lodz, 92-215 Lodz, Poland.
Department of Clinical Pharmacology, Medical University of Lodz, 90-153 Lodz, Poland.
Int J Mol Sci. 2023 Jul 11;24(14):11307. doi: 10.3390/ijms241411307.
Oxidative stress is one of the pillars crucial in the development of a non-alcoholic fatty liver disease (NAFLD) and may cause DNA damage. Since the main pathway responsible for the repair of oxidative DNA damage is the base-excision repair (BER) pathway, we examined the relationship between the presence of different genetic variants of BER-associated genes and the risk of NAFLD. The study evaluates seven single nucleotide polymorphisms (SNPs) within five genes, , , , , , in 150 NAFLD patients and 340 healthy controls. The genotyping was performed using TaqMan probes and the results were presented as odds ratio with its corresponding 95% confidence interval. The following SNPs were assessed in the study: hOGG1 (rs1052133), APEX1 (rs176094 and rs1130409), NEIL1 (rs4462560), LIG3 (rs1052536), LIG3 (rs4796030), and LIG1 (rs20579). Four of the investigated SNPs, i.e., rs176094, rs1130409, rs4462560 and rs4796030, were found to be associated with NAFLD risk. Furthermore, the occurrence of insulin resistance in patients with steatosis depended on various LIG3 genetic variants. The findings imply the impact of genes involved in BER on NAFLD and fatty liver-related insulin sensitivity.
氧化应激是导致非酒精性脂肪性肝病 (NAFLD) 的关键因素之一，可能导致 DNA 损伤。由于负责修复氧化 DNA 损伤的主要途径是碱基切除修复 (BER) 途径，因此我们研究了 BER 相关基因的不同遗传变异体的存在与 NAFLD 风险之间的关系。该研究评估了五个基因中的七个单核苷酸多态性 (SNP)，即 、 、 、 、 和 ，在 150 例 NAFLD 患者和 340 例健康对照者中。采用 TaqMan 探针进行基因分型，结果以比值比及其相应的 95%置信区间表示。该研究评估了以下 SNPs：hOGG1（rs1052133）、APEX1（rs176094 和 rs1130409）、NEIL1（rs4462560）、LIG3（rs1052536）、LIG3（rs4796030）和 LIG1（rs20579）。研究发现，在所研究的 4 个 SNP 中，即 rs176094、rs1130409、rs4462560 和 rs4796030，与 NAFLD 风险相关。此外，脂肪变性患者的胰岛素抵抗的发生取决于各种 LIG3 遗传变异体。这些发现表明参与 BER 的基因对 NAFLD 和与脂肪性肝病相关的胰岛素敏感性有影响。
