Guinotte Cheryl L, Burns Michael G, Axume Juan A, Hata Hiroko, Urrutia Tania F, Alamilla Aaron, McCabe Dale, Singgih Anny, Cogger Edward A, Caudill Marie A
Human Nutrition and Food Science Department, Cal Poly Pomona University, Pomona, CA 91768, USA.
J Nutr. 2003 May;133(5):1272-80. doi: 10.1093/jn/133.5.1272.
A common genetic variant in the methylenetetrahydrofolate reductase (MTHFR) gene involving a cytosine to thymidine (C-->T) transition at nucleotide 677 is associated with reduced enzyme activity, altered folate status and potentially higher folate requirements. The objectives of this study were to investigate the effect of the MTHFR 677 T allele on folate status variables in Mexican women (n = 43; 18-45 y) and to assess the adequacy of the 1998 folate U.S. Recommended Dietary Allowance (RDA), 400 micro g/d as dietary folate equivalents (DFE). Subjects (14 CC, 12 CT, 17 TT genotypes) consumed a low folate diet (135 micro g/d DFE) for 7 wk followed by repletion with 400 micro g/d DFE (7 CC, 6 CT, 9 TT) or 800 micro g/d DFE (7 CC, 6 CT, 8 TT) for 7 wk. Throughout repletion with 400 micro g/d DFE, the TT genotype had lower (P </= 0.05) serum folate and higher (P </= 0.05) plasma total homocysteine (tHcy) concentrations than the CC genotype. CT heterozygotes did not differ (P > 0.05) in their response relative to the CC genotype. Throughout repletion with 800 micro g/d DFE, the CT genotype had lower (P </= 0.05) serum folate concentrations and excreted less (P </= 0.05) urinary folate than the CC genotype. However, there were no differences (P > 0.05) in the measured variables between the TT and CC genotypes. Repletion with 400 micro g/d DFE led to normal blood folate and desirable plasma tHcy concentrations, regardless of MTHFR C677T genotype. Collectively, these data demonstrate that the MTHFR C-->T variant modulates folate status response to controlled folate intakes and support the adequacy of the 1998 folate U.S. RDA for all three MTHFR C677T genotypes.
亚甲基四氢叶酸还原酶（MTHFR）基因中一个常见的基因变异，涉及核苷酸677处胞嘧啶到胸腺嘧啶（C→T）的转变，与酶活性降低、叶酸状态改变以及潜在的更高叶酸需求相关。本研究的目的是调查MTHFR 677 T等位基因对墨西哥女性（n = 43；18 - 45岁）叶酸状态变量的影响，并评估1998年美国叶酸推荐膳食摄入量（RDA）400μg/d膳食叶酸当量（DFE）是否充足。受试者（14例CC基因型、12例CT基因型、17例TT基因型）先食用低叶酸饮食（135μg/d DFE）7周，随后分别补充400μg/d DFE（7例CC基因型、6例CT基因型、9例TT基因型）或800μg/d DFE（7例CC基因型、6例CT基因型、8例TT基因型）7周。在整个400μg/d DFE补充期间，TT基因型的血清叶酸浓度低于（P≤0.05）CC基因型，血浆总同型半胱氨酸（tHcy）浓度高于（P≤0.05）CC基因型。CT杂合子相对于CC基因型的反应无差异（P>0.05）。在整个800μg/d DFE补充期间，CT基因型的血清叶酸浓度低于（P≤0.05）CC基因型，尿叶酸排泄量少于（P≤0.05）CC基因型。然而，TT和CC基因型之间的测量变量无差异（P>0.05）。无论MTHFR C677T基因型如何，补充400μg/d DFE均可使血液叶酸正常，血浆tHcy浓度达到理想水平。总体而言，这些数据表明MTHFR C→T变异调节了对控制叶酸摄入量的叶酸状态反应，并支持1998年美国叶酸RDA对所有三种MTHFR C677T基因型的充足性。
