Interactions among polymorphisms in folate-metabolizing genes and serum total homocysteine concentrations in a healthy elderly population
Interactions among polymorphisms in folate-metabolizing genes and serum total homocysteine concentrations in a healthy elderly population
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DOI：
10.1093/ajcn.83.3.708
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发表时间：
2006-03-01
影响因子：
7.1
通讯作者：
Halsted, CH
中科院分区：
文献类型：
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作者：
Devlin, AM;Clarke, R;Halsted, CH
背景：同型半胱氨酸浓度受维生素状态和遗传学的影响，尤其是叶酸代谢基因的几种多态。目的：我们研究了以下叶酸代谢基因：亚甲基四氢叶酸还原酶(MTHFR)、还原型叶酸载体I(RFc1)和谷氨酸羧基肽酶II(GCPII)的多态与血清总同型半胱氨酸(THcy)和叶酸浓度的交互作用和相关性。设计：从英国牛津随机选择健康志愿者(男性436人，女性606人；平均年龄77.9岁)。我们研究了MTHFR677C-&Gt；T、MTHFR1298A-&Gt；C、RFC180G-&Gt；A和GCPII1561C-&Gt；T等位基因对血清tHcy和叶酸浓度的个体效应及其交互作用。结果：携带MTHFR677TT基因型者的血清tHcy浓度高于携带MTHFR677CC基因型者(P<；0.001)，且这种影响在叶酸水平较低的人群中更明显(P=0.026)。MTHFR 1298A-&Gt；C、Rfc1 8OG-&Gt；A和GCPII 1561C-&Gt；T多态对血清tHcy或叶酸浓度无个体影响。MTHFR 677C->；T和MTHFR 1298A-gt；C多态对tHcy浓度无交互作用。MTHFR677TT和Rfc1 80GG基因型之间存在交互作用(P=0.0 5)，携带该基因组合的个体的血清tHcy浓度(+/-SEM)平均值(18.5+/-1.2mU mol/L)比全人群平均值(13.4+/-0.2 mU mol/L)高5.1mU mol/L。结论：叶酸和tHcy浓度不受MTHFR 12 98A和GT；C、Rfc1 80G和GT；A或GCPII 1561C>；T组合的单独影响T和MTHFR 1298A->；C等位基因。观察到MTHFR 677TT和Rfc1 80GG基因型之间存在交互作用，具有这种组合的人血清tHcy水平较高。
Background: Homocysteine concentrations are influenced by vitamin status and genetics, especially several polymorphisms in folate-metabolizing genes.Objective: We examined the interactions and associations with serum total homocysteine (tHcy) and folate concentrations of polymorphisms in the following folate-metabolizing genes: methylenetetrahydrofolate, reductase (MTHFR), reduced folate carrier I (RFC1), and glutamate carboxypeptidase II (GCPII).Design: Healthy volunteers (436 men and 606 women; mean age: 77.9 y) were randomly selected from among residents of Oxford, United Kingdom. We determined the individual effects and interactions of the MTHFR 677C -> T, MTHFR 1298A -> C, RFC1 80G -> A, and GCPII 1561C -> T polymorphisms on serum tHcy and folate concentrations.Results: Subjects with the MTHFR 677TT genotype had higher serum tHcy concentrations than did those with the MTHFR 677CC genotype(P < 0.001), and this effect was greater in subjects with low serum folate status (P for interaction=0.026). The MTHFR 1298A -> C, RFC1 8OG -> A, and GCPII 1561C -> T polymorphisms had no individual effects on serum tHcy or folate concentrations. There was no interactive effect of the MTHFR 677C -> T and MTHFR 1298A -> C polymorphisms on tHcy concentrations. An interaction (P=0.05) was observed between the MTHFR 677TT and RFC1 80GG genotypes, whereby persons with this genotype combination had a mean (+/- SEM) serum tHcy concentration (18.5 +/- 1.2 mu mol/L) that was 5.1 mu mol/L greater than the mean value of 13.4 +/- 0.2 mu mol/L for the whole population.Conclusions: Folate and tHcy concentrations were not affected individually by the MTHFR 1298A -> C, RFC1 80G -> A, or GCPII 1561C -> T polymorphisms or by combinations of the MTHFR 677C -> T and MTHFR 1298A -> C genotypes. An interaction between the MTHFR 677TT and RFC1 80GG genotypes was observed whereby persons with this combination had higher serum tHcy.