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首页> 外文期刊>Genes and Nutrition >Effects of methionine synthase and methylenetetrahydrofolate reductase gene polymorphisms on markers of one-carbon metabolism
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Effects of methionine synthase and methylenetetrahydrofolate reductase gene polymorphisms on markers of one-carbon metabolism

机译：蛋氨酸合酶和亚甲基四氢叶酸还原酶基因多态性对一碳代谢标志物的影响

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摘要

Genetic and nutritional factors play a role in determining the functionality of the one-carbon (1C) metabolism cycle, a network of biochemical reactions critical to intracellular processes. Genes encoding enzymes for methylenetetrahydrofolate reductase (MTHFR) and methionine synthase (MTR) may determine biomarkers of the cycle including homocysteine (HCY), S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH). MTHFR C677T is an established genetic determinant of HCY but less is known of its effect on SAM and SAH. Conversely, the relationship between MTR A2756G and HCY remains inconclusive, and its effect on SAM and SAH has only been previously investigated in a female-specific population. Folate and vitamin B12 are essential substrate and cofactor of 1C metabolism; thus, consideration of gene–nutrient interactions may clarify the role of genetic determinants of HCY, SAM and SAH. This cross-sectional study included 570 healthy volunteers from Kingston, Ontario, Ottawa, Ontario and Halifax, Nova Scotia, Canada. Least squares regression was used to examine the effects of MTR and MTHFR polymorphisms on plasma HCY, SAM and SAH concentrations; gene–gene and gene–nutrient interactions were considered with the inclusion of cross-products in the model. Main effects of MTR and MTHFR polymorphisms on HCY concentrations were observed; however, no gene–gene or gene–nutrient interactions were found. No association was observed for SAM. For SAH, interactions between MTR and MTHFR polymorphisms, and MTHFR polymorphism and serum folate were found. The findings of this research provide evidence that HCY and SAH, biomarkers of 1C metabolism, are influenced by genetic and nutritional factors and their interactions.
机译：遗传和营养因素在决定一碳（1C）代谢循环（对细胞内过程至关重要的生化反应网络）的功能中起作用。编码亚甲基四氢叶酸还原酶（MTHFR）和蛋氨酸合酶（MTR）的酶的基因可以确定该周期的生物标记，包括高半胱氨酸（HCY），S-腺苷甲硫氨酸（SAM）和S-腺苷同型半胱氨酸（SAH）。 MTHFR C677T是HCY的既定遗传决定因素，但对其对SAM和SAH的影响知之甚少。相反，MTR A2756G与HCY之间的关系尚无定论，其对SAM和SAH的作用以前仅在女性特定人群中进行过研究。叶酸和维生素B12是1C代谢必不可少的底物和辅因子。因此，考虑基因与营养的相互作用可以阐明HCY，SAM和SAH的遗传决定因素的作用。这项横断面研究包括来自安大略省金斯敦，安大略省渥太华和加拿大新斯科舍省哈利法克斯的570名健康志愿者。最小二乘回归用于检验MTR和MTHFR多态性对血浆HCY，SAM和SAH浓度的影响。在模型中考虑了交叉产物，考虑了基因-基因和基因-营养相互作用。观察到MTR和MTHFR多态性对HCY浓度的主要影响。但是，没有发现基因与基因或基因与营养的相互作用。没有观察到SAM的关联。对于SAH，发现了MTR和MTHFR多态性之间的相互作用，以及MTHFR多态性和血清叶酸。这项研究的发现提供了证据，表明HCY和SAH是1C代谢的生物标记，受遗传和营养因素及其相互作用的影响。

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