Department of Public Health Sciences, Queen's University, Carruthers Hall, Kingston, ON, K7L3N6, Canada.
Genes Nutr. 2013 Nov;8(6):571-80. doi: 10.1007/s12263-013-0358-2. Epub 2013 Oct 8.
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.
遗传和营养因素在决定一碳（1C）代谢循环的功能中起着作用，这是一个对细胞内过程至关重要的生化反应网络。编码亚甲基四氢叶酸还原酶（MTHFR）和蛋氨酸合成酶（MTR）的基因可能决定循环的生物标志物，包括同型半胱氨酸（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 SAM 和 SAH 的影响知之甚少。相反，MTR A2756G 与 HCY 之间的关系仍不确定，其对 SAM 和 SAH 的影响之前仅在女性特异性人群中进行了研究。叶酸和维生素 B12 是 1C 代谢的必需底物和辅助因子；因此，考虑基因-营养相互作用可能会阐明 HCY、SAM 和 SAH 的遗传决定因素的作用。本横断面研究包括来自加拿大安大略省金斯顿、安大略省渥太华和新斯科舍省哈利法克斯的 570 名健康志愿者。最小二乘法回归用于研究 MTR 和 MTHFR 多态性对血浆 HCY、SAM 和 SAH 浓度的影响；考虑到基因-基因和基因-营养相互作用，并在模型中包含交叉乘积。观察到 MTR 和 MTHFR 多态性对 HCY 浓度的主要影响；然而，没有发现基因-基因或基因-营养相互作用。未观察到 SAM 的关联。对于 SAH，发现了 MTR 和 MTHFR 多态性之间以及 MTHFR 多态性和血清叶酸之间的相互作用。这项研究的结果提供了证据，表明 HCY 和 SAH，1C 代谢的生物标志物，受遗传和营养因素及其相互作用的影响。
