Inoue-Choi Maki, Nelson Heather H, Robien Kim, Arning Erland, Bottiglieri Teodoro, Koh Woon-Puay, Yuan Jian-Min
Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, Minnesota, United States.
Int J Mol Epidemiol Genet. 2012;3(2):160-73. Epub 2012 May 15.
S-adenosylmethionine (SAM) is a primary methyl donor for the methylation of many molecules including DNA. DNA methylation is believed to play an important role in functions of cells and genes. Dietary, genetic and metabolic factors that influence systematic SAM levels are not fully understood. We conducted cross-sectional analysis to evaluate associations between plasma concentrations of one-carbon metabolism nutrients and metabolites and plasma SAM concentrations using healthy individuals within the Singapore Chinese Health Study. Plasma SAM, betaine, choline, folate, total homocysteine (Hcy), methionine, S-adenosylhomocysteine (SAH), vitamin B(6) and vitamin B(12) concentrations were quantified. Genotypes of methionine adenosyltransferases (MAT1A, MAT2A and MAT2B) were also determined. Linear regression and path analysis were performed to depict the directed dependencies in one-carbon metabolism. Age and body mass index were positively associated while cigarette smoking were inversely associated with plasma SAM concentrations. Plasma choline, methionine and SAH were positively and strongly associated with plasma SAM after adjustment for confounders. Plasma betaine and folate were positively associated with plasma SAM only in men. Men carrying the variant MAT1A genotypes had lower plasma SAM concentrations than men carrying the wild type genotype (p for gene x gender interaction = 0.02). This effect modification by gender was restricted to individuals with low plasma methionine. In conclusion, plasma choline, methionine and SAH were strongly associated with plasma SAM concentrations. The MAT1A genetic polymorphism may impact plasma SAM concentrations in men with low plasma methionine concentrations.
S-腺苷甲硫氨酸(SAM)是包括DNA在内的许多分子甲基化的主要甲基供体。DNA甲基化被认为在细胞和基因功能中起重要作用。影响全身SAM水平的饮食、遗传和代谢因素尚未完全了解。我们进行了横断面分析,以评估新加坡华人健康研究中健康个体的一碳代谢营养素和代谢物血浆浓度与血浆SAM浓度之间的关联。对血浆SAM、甜菜碱、胆碱、叶酸、总同型半胱氨酸(Hcy)、甲硫氨酸、S-腺苷同型半胱氨酸(SAH)、维生素B6和维生素B12浓度进行了定量。还测定了甲硫氨酸腺苷转移酶(MAT1A、MAT2A和MAT2B)的基因型。进行线性回归和路径分析以描述一碳代谢中的直接依赖性。年龄和体重指数与血浆SAM浓度呈正相关,而吸烟与血浆SAM浓度呈负相关。调整混杂因素后,血浆胆碱、甲硫氨酸和SAH与血浆SAM呈正相关且相关性较强。血浆甜菜碱和叶酸仅在男性中与血浆SAM呈正相关。携带MAT1A变异基因型的男性血浆SAM浓度低于携带野生型基因型的男性(基因×性别相互作用的p值 = 0.02)。这种性别效应修饰仅限于血浆甲硫氨酸水平低的个体。总之,血浆胆碱、甲硫氨酸和SAH与血浆SAM浓度密切相关。MAT1A基因多态性可能影响血浆甲硫氨酸浓度低的男性的血浆SAM浓度。