The effect of 677C → T and 1298A → C mutations on plasma homocysteine and 5,10-methylenetetrahydrofolate reductase activity in healthy subjects
The effect of 677C → T and 1298A → C mutations on plasma homocysteine and 5,10-methylenetetrahydrofolate reductase activity in healthy subjects
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DOI：
10.1017/s0007114500000751
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发表时间：
2000-06-01
影响因子：
3.6
通讯作者：
Nicolas, JP
中科院分区：
文献类型：
--
作者：
Chango, A;Boisson, F;Nicolas, JP
我们研究了66名年龄在27-47岁的健康法国受试者的亚甲基四氢叶酸还原酶（MTHFR）基因的常见突变（677 C-> T和1298 A-> C）的影响。测定血清叶酸、维生素B-12和血浆总同型半胱氨酸以及淋巴细胞中MTHFR的比活性。677 TT基因型纯合子的频率为18%，1298 CC基因型纯合子的频率为12.5%。两种突变杂合子的个体频率为23.5%。1298 A--> C突变与677 CC和677 CT基因型受试者MTHFR比活性降低相关。与677 CC/1298 AA基因型的MTHFR比活性相比，677 CC/1298 AC基因型的该活性为60%，677 CC/1298 CC基因型的该活性为52%。两种突变的杂合子（677 CT/1298 AC基因型）具有参考比活性的36%。虽然677 TT和1298 CC基因型受试者的同型半胱氨酸水平高于其他基因型受试者，但不同基因型之间没有观察到显著差异。这可能是由于高血清叶酸水平在我们的样本中，并表明，叶酸治疗可能是有用的，以防止高同型半胱氨酸血症的纯合子突变的主题。
We have studied the effect of common mutations (677C --> T and 1298A --> C) of the methylenetetrahydrofolate reductase (MTHFR) gene in sixty-six healthy French subjects, aged 27-47 years. Serum folate, vitamin B-12, and plasma total homocysteine were measured as well as the specific activity of MTHFR in lymphocytes. The frequency of subjects homozygous for the 677TT genotype was 18 %, and that of those homozygous for the 1298CC genotype was 12.5 %. The frequency of individuals heterozygous for both mutations was 23.5 %. The 1298A --> C mutation was associated with decreased MTHFR specific activity in subjects with both 677CC and 677CT genotypes. This activity was 60 % for the 677CC/1298AC genotype and 52 % for the 677CC/1298CC genotype when compared with the MTHFR specific activity of the 677CC/1298AA genotype. Heterozygotes for both mutations (677CT/1298AC genotype) had 36 % of the reference specific activity. Although homocysteine levels in 677TT and 1298CC genotype subjects were higher than for other genotypes, no significant differences were observed among different genotypes. This may be due to high serum folate level in our samples, and suggests that folate therapy may be useful to prevent hyperhomocysteinaemia in homozygous mutant subjects.