Choi Youngjin, Kwon Hyuk-Ku, Park Sunmin
Department of Food Science & Technology, Hoseo University, Asan 31499, Republic of Korea.
Department of Environmental Engineering, Hoseo University, Asan 31499, Republic of Korea.
Antioxidants (Basel). 2023 Jun 15;12(6):1280. doi: 10.3390/antiox12061280.
Oxidative stress is associated with insulin resistance and secretion, and antioxidant systems are essential for preventing and managing type 2 diabetes (T2DM). This study aimed to explore the polygenic variants linked to oxidative stress and the antioxidant system among those associated with T2DM and the interaction of their polygenic risk scores (PRSs) with lifestyle factors in a large hospital-based cohort ( = 58,701). Genotyping, anthropometric, biochemical, and dietary assessments were conducted for all participants with an average body mass index of 23.9 kg/m. Genetic variants associated with T2DM were searched through genome-wide association studies in participants with T2DM ( = 5383) and without T2DM ( = 53,318). The Gene Ontology database was searched for the antioxidant systems and oxidative stress-related genes among the genetic variants associated with T2DM risk, and the PRS was generated by summing the risk alleles of selected ones. Gene expression according to the genetic variant alleles was determined on the FUMA website. Food components with low binding energy to the GSTA5 protein generated from the wildtype and mutated _ (missense mutation) genes were selected using in silico analysis. Glutathione metabolism-related genes, including glutathione peroxidase ( and , glutathione disulfide reductase (, peroxiredoxin-6 (, glutamate-cysteine ligase catalytic subunit (, glutathione S-transferase alpha-5 (, and gamma-glutamyltransferase-1 (), were predominantly selected with a relevance score of >7. The PRS related to the antioxidant system was positively associated with T2DM (ORs = 1.423, 95% CI = 1.22-1.66). The active site of the GASTA proteins having valine or leucine at 55 due to the missense mutation ( had a low binding energy (<-10 kcal/mol) similarly or differently to some flavonoids and anthocyanins. The PRS interacted with the intake of bioactive components (specifically dietary antioxidants, vitamin C, vitamin D, and coffee) and smoking status ( < 0.05). In conclusion, individuals with a higher PRS related to the antioxidant system may have an increased risk of T2DM, and there is a potential indication that exogenous antioxidant intake may alleviate this risk, providing insights for personalized strategies in T2DM prevention.
氧化应激与胰岛素抵抗及分泌相关，抗氧化系统对于预防和管理2型糖尿病（T2DM）至关重要。本研究旨在探索在一个大型医院队列（n = 58,701）中，与T2DM相关的氧化应激和抗氧化系统相关的多基因变异，以及它们的多基因风险评分（PRSs）与生活方式因素的相互作用。对所有平均体重指数为23.9 kg/m²的参与者进行基因分型、人体测量、生化和饮食评估。通过全基因组关联研究在患有T2DM（n = 5383）和未患有T2DM（n = 53,318）的参与者中搜索与T2DM相关的基因变异。在与T2DM风险相关的基因变异中，在基因本体数据库中搜索抗氧化系统和氧化应激相关基因，并通过对选定基因的风险等位基因求和生成PRS。根据基因变异等位基因的基因表达在FUMA网站上确定。使用计算机分析选择与野生型和突变型_（错义突变）基因产生的GSTA5蛋白结合能低的食物成分。主要选择了与谷胱甘肽代谢相关的基因，包括谷胱甘肽过氧化物酶（和）、谷胱甘肽二硫化物还原酶（）、过氧化物酶体增殖物激活受体6（）、谷氨酸-半胱氨酸连接酶催化亚基（）、谷胱甘肽S-转移酶α-5（）和γ-谷氨酰转移酶-1（），相关性得分>7。与抗氧化系统相关的PRS与T2DM呈正相关（ORs = 1.423, 95% CI = 1.22 - 1.66）。由于错义突变在55位具有缬氨酸或亮氨酸的GASTA蛋白的活性位点与一些黄酮类化合物和花青素类似或不同，具有低结合能（<-10 kcal/mol）。PRS与生物活性成分（特别是膳食抗氧化剂、维生素C、维生素D和咖啡）的摄入量以及吸烟状态相互作用（P < 0.05）。总之，与抗氧化系统相关的PRS较高的个体患T2DM的风险可能增加，并且有潜在迹象表明外源性抗氧化剂的摄入可能减轻这种风险，为T2DM预防的个性化策略提供了见解。
