MTHFR677C → T genotype modulates the effect of a 5-year supplementation with B-vitamins on homocysteine concentration: The SU.FOL.OM3 randomized controlled trial

AimsTo study how MTHFR 677C→T genotype modulates the effect of supplementation with B-vitamins on total homocysteine (tHcy) and B-vitamin concentrations.Methods2381 patients with a personal history of cardiovascular disease were randomly assigned to one of four groups: 1) B-vitamins alone (560 μg of 5-methyl-THF, 3 mg of vitamin B6 and 20 μg of vitamin B12), 2) n-3 fatty acids alone (600 mg of EPA and DHA in a 2:1 ratio), 3) B-vitamins and n-3 fatty acids, and 4) placebo. Participants were followed up for 4.7 years. At baseline and annually thereafter, biological parameters were assessed. Multivariate and linear mixed models were fit to study the interaction between B-vitamins and MTHFR genotype.ResultsAmong supplemented participants, concentrations of all three B-vitamins increased during the first year (all pMTHFR genotype categories. tHcy decreased by 26.3% during the first year (ptrendTT than among CT or CC subjects (pinteractionTT homozygous and CC homozygous subjects was 2.33 μmol/l (pConclusionParticipants with the TT genotype exhibited a lower 5-year decrease in tHcy concentrations following a B-vitamin supplementation than did participants with the CC or CT genotype.Clinical trial registrationCurrent Controlled Trials # ISRCTN41926726.

研究目的：探讨亚甲基四氢叶酸还原酶（MTHFR）677C→T基因型对B族维生素补充干预总同型半胱氨酸（tHcy）及B族维生素浓度的调控作用。
研究方法：纳入2381例有心血管疾病个人史的患者，随机分为4组：1）单纯B族维生素补充组（560 μg 5-甲基四氢叶酸、3 mg 维生素B6及20 μg 维生素B12）；2）单纯n-3脂肪酸补充组（比例为2:1的600 mg EPA（二十碳五烯酸）与DHA（二十二碳六烯酸））；3）B族维生素联合n-3脂肪酸补充组；4）安慰剂组。受试者随访时长为4.7年，于基线及此后每年检测生物学参数。采用多因素线性混合模型分析B族维生素与MTHFR基因型的交互作用。
研究结果：在接受补充干预的受试者中，3种B族维生素的浓度在第一年均出现升高（所有p值均符合MTHFR基因型分类特征）。第一年总同型半胱氨酸浓度下降26.3%，且TT基因型受试者的下降幅度低于CT或CC基因型受试者（交互作用p值）；TT纯合子与CC纯合子受试者的浓度差值为2.33 μmol/L。
研究结论：与CC或CT基因型受试者相比，TT基因型受试者在接受B族维生素补充后，5年内总同型半胱氨酸浓度的下降幅度更低。
临床试验注册：Current Controlled Trials # ISRCTN41926726。