School of Public Health, Capital Medical University, Beijing, PR China.
Suzhou Science & Technology Town Hospital, Suzhou, Jiangsu, PR China.
Exp Gerontol. 2023 Jul;178:112208. doi: 10.1016/j.exger.2023.112208. Epub 2023 May 23.
Plasma folate levels are closely related to antioxidant capacity and are regulated by folate pathway gene polymorphism. However, few studies have explored the gender-specific association of folate pathway gene polymorphism with oxidative stress biomarkers. The present study was designed to explore the gender-specific independent and combined impacts of solute carrier family 19 member 1 (SLC19A1) and methylenetetrahydrofolate reductase (MTHFR) genetic polymorphisms on oxidative stress biomarkers in older adults.
A total of 401 subjects were recruited, including 145 males and 256 females. Demographic characteristics of the participants were collected by using a self-administered questionnaire. Fasting venous blood samples were taken for folate pathway gene genotyping, circulating lipids parameters and erythrocyte oxidative stress biomarkers measurement. The difference of genotype distribution and the Hardy-Weinberg equilibrium was calculated by the Chi-square test. The general linear model was applied to compare the plasma folate levels and erythrocyte oxidative stress biomarkers. Multiple linear regression was used to explore the correlation between genetic risk scores and oxidative stress biomarkers. Logistic regression was used to explore the association of genetic risk scores of folate pathway gene with folate deficiency.
The male subjects have lower plasma folate and HDL-C levels than the female ones, and the male carrying MTHFR rs1801133 (CC) or MTHFR rs2274976 (GA) genotypes have higher erythrocyte SOD activity. The plasma folate levels, erythrocyte SOD and GSH-PX activities were negatively correlated with genetic risk scores in the male subjects. A positive correlation between the genetic risk scores and folate deficiency was observed in the male subjects.
There was association between folate pathway gene polymorphism of Solute Carrier Family 19 Member 1 (SLC19A1) and Methylenetetrahydrofolate Reductase (MTHFR) with erythrocyte SOD and GSH-PX activities, and folate levels in male but not in female aging subjects. Genetic variant of genes involved in folate metabolism has strong impact on plasma folate levels in the male aging subjects. Our data demonstrated that there was a potential interaction of gender and its genetic background in affecting the body's antioxidant capacity and the risk of folate deficiency in aging subjects.
血浆叶酸水平与抗氧化能力密切相关，并受叶酸途径基因多态性调节。然而，很少有研究探讨叶酸途径基因多态性与氧化应激生物标志物的性别特异性关联。本研究旨在探讨溶质载体家族 19 成员 1（SLC19A1）和亚甲基四氢叶酸还原酶（MTHFR）基因遗传多态性对老年男性和女性氧化应激生物标志物的性别特异性独立和联合影响。
共招募 401 名受试者，包括 145 名男性和 256 名女性。采用自填式问卷收集参与者的人口统计学特征。采集空腹静脉血进行叶酸途径基因分型、循环血脂参数和红细胞氧化应激生物标志物检测。采用卡方检验计算基因型分布和哈迪-温伯格平衡的差异。采用一般线性模型比较血浆叶酸水平和红细胞氧化应激生物标志物。采用多元线性回归分析遗传风险评分与氧化应激生物标志物的相关性。采用逻辑回归分析叶酸途径基因遗传风险评分与叶酸缺乏的关系。
男性的血浆叶酸和高密度脂蛋白胆固醇水平低于女性，携带 MTHFR rs1801133（CC）或 MTHFR rs2274976（GA）基因型的男性红细胞 SOD 活性较高。男性血浆叶酸水平、红细胞 SOD 和 GSH-PX 活性与遗传风险评分呈负相关。男性遗传风险评分与叶酸缺乏呈正相关。
在男性衰老受试者中，溶质载体家族 19 成员 1（SLC19A1）和亚甲基四氢叶酸还原酶（MTHFR）的叶酸途径基因多态性与红细胞 SOD 和 GSH-PX 活性以及叶酸水平相关，而在女性衰老受试者中则无相关性。涉及叶酸代谢的基因的遗传变异对男性衰老受试者的血浆叶酸水平有很大影响。我们的数据表明，性别及其遗传背景在影响机体抗氧化能力和衰老受试者叶酸缺乏风险方面存在潜在的相互作用。
