Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, and National Yang-Ming University School of Medicine, Taipei, Taiwan, ROC.
J Chin Med Assoc. 2021 Jan 1;84(1):14-18. doi: 10.1097/JCMA.0000000000000437.
Nonalcoholic steatohepatitis (NASH) is closely related to reactive oxygen species (ROS). Superoxide anion radicals, the main product of ROS, can be reduced by manganese superoxide dismutase (SOD2) to hydrogen peroxide, which is further reduced by catalase (CAT) and glutathione peroxidase (GPX) to water. We aimed to investigate the association between the most important genetic variants of SOD2, CAT, and GPX1 and susceptibility to NASH.
A total of 126 adults with liver tissue-verified NASH, 56 patients with liver tissue-verified nonalcoholic fatty liver (NAFL), and 153 healthy controls were enrolled. Their DNA profiles were retrieved for genotype assessment of SOD2 47T>C (rs4880), CAT -262C>T (rs1001179), and GPX1 593C>T (rs1050450) variation.
There were statistical differences between the SOD2 and CAT genotypes across the NASH, NAFL, and control groups, but not GPX1. The NASH group had a significantly higher frequency of subjects with SOD2 C allele (38.8%) compared with the NASL group (25.0%) and the controls (22.9%, p = 0.010). Similarly, the NASH group had a significantly higher percentage of subjects with CAT T allele (23.0%) compared with the NAFL group (10.7%) and the controls (7.2%, p = 0.001). For subjects with both the SOD2 C allele and CAT T allele, 88.2% were in the NASH group. After adjusting for confounders, the CAT mutant T allele and SOD2 mutant C allele were still the highest independent risk factors for NASH (odds ratio [OR] 3.10 and 2.36, respectively). In addition, there was a synergistic effect for those two alleles and the occurrence of NASH with an adjusted OR of 8.57 (p = 0.030).
The genetic variations of CAT and SOD2 may increase the risk of NASH, which may aid in the screening of patients who are at high risk of NASH, and offer a potential anti-oxidant targeting route for the treatment of NASH.
非酒精性脂肪性肝炎（NASH）与活性氧（ROS）密切相关。超氧阴离子自由基是 ROS 的主要产物，可被锰超氧化物歧化酶（SOD2）还原为过氧化氢，然后过氧化氢进一步被过氧化氢酶（CAT）和谷胱甘肽过氧化物酶（GPX）还原为水。我们旨在研究 SOD2、CAT 和 GPX1 最重要的遗传变异与 NASH 易感性之间的关系。
共纳入 126 例经肝组织证实的 NASH 成人患者、56 例经肝组织证实的非酒精性脂肪肝（NAFL）患者和 153 例健康对照者。提取其 DNA 图谱，评估 SOD2 47T>C(rs4880)、CAT-262C>T(rs1001179)和 GPX1 593C>T(rs1050450) 变异的基因型。
NASH、NAFL 和对照组之间 SOD2 和 CAT 基因型存在统计学差异，但 GPX1 基因型无差异。与 NAFL 组（25.0%）和对照组（22.9%）相比，NASH 组 SOD2 C 等位基因（38.8%）的频率明显更高（p=0.010）。同样，与 NAFL 组（10.7%）和对照组（7.2%）相比，NASH 组 CAT T 等位基因（23.0%）的频率明显更高（p=0.001）。SOD2 C 等位基因和 CAT T 等位基因均为携带者的受试者中，88.2%为 NASH 组。校正混杂因素后，CAT 突变 T 等位基因和 SOD2 突变 C 等位基因仍然是 NASH 的最高独立危险因素（比值比[OR]分别为 3.10 和 2.36）。此外，这两个等位基因的协同作用与 NASH 的发生有协同作用，校正后的 OR 为 8.57（p=0.030）。
CAT 和 SOD2 的遗传变异可能会增加 NASH 的风险，这可能有助于筛选 NASH 高危患者，并为 NASH 的治疗提供潜在的抗氧化靶向途径。
