Thermolabile variant of 5,10-methylenetetrahydrofolate reductase associated with low red-cell folates: Implications for folate intake recommendations
Thermolabile variant of 5,10-methylenetetrahydrofolate reductase associated with low red-cell folates: Implications for folate intake recommendations
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DOI：
10.1016/s0140-6736(96)12049-3
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发表时间：
1997-05-31
期刊：
影响因子：
168.9
通讯作者：
Scott, JM
中科院分区：
文献类型：
--
作者：
Molloy, AM;Daly, S;Scott, JM
背景 叶酸的膳食参考值与其他营养素一样，针对的是一般人群和所谓的正常人群，而不是有特殊需要的人群，例如患有遗传或代谢异常或疾病的人群。然而，5-15% 的普通人群是 5,10-亚甲基四氢叶酸还原酶 (C677T) 不耐热变体的纯合子，这种变体会导致轻度高同型半胱氨酸血症，并与血管疾病的发展和神经管缺陷的风险呈正相关。如果大部分人群的组织叶酸状态因这种或其他遗传变异而受到损害，则可能需要更改目前的饮食参考值。 方法 我们鉴定了 C677T 基因型，并测量了两组健康女性（孕妇，242 名，未怀孕，318 名）的红细胞叶酸浓度。然后我们分析了基因型对红细胞叶酸的影响，红细胞叶酸是组织叶酸储存的可靠标记。结果在怀孕组中有 20 个 TT 纯合子、114 个野生型 CC 纯合子和 108 个 CT 杂合子。在非怀孕组中，数字分别为 41、148 和 129。在怀孕组和非怀孕组中，TT 纯合子女性的红细胞叶酸显着低于 CC 纯合子女性（平均 252 [95% CI 202-317] vs 347 [321-372] mu g/L，孕妇 p=0.002；284 [250-327] vs 347 [342-372] mu g/L，对于非怀孕女性，p=0.01）。在怀孕组中，TT 纯合子女性的血浆叶酸也显着低于 CC 纯合子女性 (p=0.009)，但在非怀孕组中则不然。 解释 这些结果表明，一般人群中相当少数人的叶酸需求可能增加。未来的研究可能会表明存在与特定营养素相互作用的其他常见遗传变异，并对假设任何一般人群的营养素需求“正常”的有效性提出质疑。
Background The dietary reference values for folate, as for other nutrients, are targeted to the general and supposedly normal population, not people with special needs, such as those with genetic or metabolic abnormalities or diseases. However, 5-15% of general populations are homozygous for a thermolabile variant of 5,10-methylenetetrahydrofolate reductase (C677T) which causes mild hyperhomocysteinaemia and is positively associated with the development of vascular disease and the risk of neural-tube defects. If tissue-folate status is compromised in large sectors of the population by this or other genetic variants, the present dietary reference Values may need to be changed.Methods We identified the C677T genotype and measured red-cell folate concentrations in two groups of healthy women (pregnant, 242, not pregnant, 318). We then analysed the effect of genotype on red-cell folates, which are a reliable marker for tissue folate stores.Findings In the pregnant group there were 20 TT homozygotes, 114 wild-type CC homozygotes, and 108 CT heterozygotes. In the non-pregnant group, the numbers were 41, 148, and 129. In both pregnant and non-pregnant groups, red-cell folate was significantly lower among TT homozygous than CC homozygous women (mean 252 [95% CI 202-317] vs 347 [321-372] mu g/L, p=0.002 for pregnant women; 284 [250-327] vs 347 [342-372] mu g/L, p=0.01 for non-pregnant women). Plasma folate was also significantly lower in TT homozygous than in CC homozygous women in the pregnant group (p=0.009) but not in the non-pregnant group.Interpretation These results suggest that a substantial minority of people in general populatgions may have increased folate needs. Future studies may show the presence of other common genetic variants that interact with particular nutrients and place doubts on the validity of assuming ''normality'' for nutrient requirements in any general population.