Vaughn Jaimie D, Bailey Lynn B, Shelnutt Karla P, Dunwoody Kristina M von-Castel, Maneval David R, Davis Steven R, Quinlivan Eoin P, Gregory Jesse F, Theriaque Douglas W, Kauwell Gail P A
Food Science and Human Nutrition Department, University of Florida, Gainesville, FL 32611, USA.
J Nutr. 2004 Nov;134(11):2985-90. doi: 10.1093/jn/134.11.2985.
Methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR) are important for homocysteine remethylation. This study was designed to determine the influence of genetic variants (MTHFR 677C-->T, MTHFR 1298A-->C, and MTRR 66A-->G), folate, and vitamin B-12 status on plasma homocysteine in women (20-30 y; n = 362). Plasma homocysteine was inversely (P < 0.0001) associated with serum folate and plasma vitamin B-12 regardless of genotype. Plasma homocysteine was higher (P < 0.05) for women with the MTHFR 677 TT/1298 AA genotype combination compared with the CC/AA, CC/AC, and CT/AA genotypes. Women with the MTHFR 677 TT/MTRR 66 AG genotype had higher (P < 0.05) plasma homocysteine than all other genotype combinations except the TT/AA and TT/GG genotypes. There were 5.4-, 4.3-, and 3.8-fold increases (P < 0.001) in risk for plasma homocysteine in the top 5, 10, and 20%, respectively, of the homocysteine distribution for subjects with the MTHFR 677 TT compared with the CC and CT genotypes. Predicted plasma homocysteine was inversely associated with serum folate (P = 0.003) and plasma vitamin B-12 (P = 0.002), with the degree of correlation dependent on MTHFR 677C-->T genotype. These data suggest that coexistence of the MTHFR 677 TT genotype with the MTRR 66A-->G polymorphism may exacerbate the effect of the MTHFR variant alone. The potential negative effect of combined polymorphisms of the MTHFR and MTRR genes on plasma homocysteine in at-risk population groups with low folate and/or vitamin B-12 status, such as women of reproductive potential, deserves further investigation.
亚甲基四氢叶酸还原酶（MTHFR）和甲硫氨酸合酶还原酶（MTRR）对同型半胱氨酸的再甲基化很重要。本研究旨在确定基因变异（MTHFR 677C→T、MTHFR 1298A→C和MTRR 66A→G）、叶酸和维生素B-12状态对20至30岁女性（n = 362）血浆同型半胱氨酸的影响。无论基因型如何，血浆同型半胱氨酸均与血清叶酸和血浆维生素B-12呈负相关（P < 0.0001）。与CC/AA、CC/AC和CT/AA基因型相比，MTHFR 677 TT/1298 AA基因型组合的女性血浆同型半胱氨酸水平更高（P < 0.05）。与除TT/AA和TT/GG基因型外的所有其他基因型组合相比，MTHFR 677 TT/MTRR 66 AG基因型的女性血浆同型半胱氨酸水平更高（P < 0.05）。与CC和CT基因型相比，MTHFR 677 TT基因型的受试者在同型半胱氨酸分布最高的5%、10%和20%中，血浆同型半胱氨酸风险分别增加了5.4倍、4.3倍和3.8倍（P < 0.001）。预测的血浆同型半胱氨酸与血清叶酸（P = 0.003）和血浆维生素B-12（P = 0.002）呈负相关，相关程度取决于MTHFR 677C→T基因型。这些数据表明，MTHFR 677 TT基因型与MTRR 66A→G多态性共存可能会加剧MTHFR变异单独产生的影响。MTHFR和MTRR基因联合多态性对叶酸和/或维生素B-12水平较低的高危人群（如有生殖潜力的女性）血浆同型半胱氨酸的潜在负面影响值得进一步研究。
