A second genetic polymorphism in methylenetetrahydrofolate reductase (MTHFR) associated with decreased enzyme activity
A second genetic polymorphism in methylenetetrahydrofolate reductase (MTHFR) associated with decreased enzyme activity
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DOI：
10.1006/mgme.1998.2714
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发表时间：
1998-07-01
影响因子：
3.8
通讯作者：
Rozen, R
中科院分区：
文献类型：
--
作者：
Weisberg, I;Tran, P;Rozen, R
亚甲基四氢叶酸还原酶（MTHFR）中的常见突变C677 T导致活性降低的热不稳定变体。纯合子突变个体（约10%的北美人）易患轻度高同型半胱氨酸血症，当他们的叶酸水平低时。这种遗传-营养相互作用被认为会增加神经管缺陷和血管疾病的风险。在这次交流中，我们描述了MTHFR（A1298 C）中的第二个常见变体，即E到A的替换。在大约10%的加拿大人中观察到纯合子。这种多态性与酶活性降低有关;纯合子在淋巴细胞中具有约60%的对照活性。C677 T和A1298 C突变的杂合子，约15%的个体，具有50-60%的对照活性，该值低于C677 T变体的单个杂合子中所见的值。没有个体是两种突变的纯合子。在C677 T突变存在和不存在的情况下，对A1298 C突变的进一步研究是必要的，以充分解决这种新的遗传变异在复杂性状中的作用。一个沉默的遗传变异，T1317 C，被确定在同一外显子。在我们的研究组中，它相对罕见（等位基因频率5%），但在非洲个体的小样本中相当常见（等位基因频率39%）。(C)北京：科学出版社.
A common mutation in methylenetetrahydrofolate reductase (MTHFR), C677T, results in a thermolabile variant with reduced activity. Homozygous mutant individuals (approximately 10% of North Americans) are predisposed to mild hyperhomocysteinemia, when their folate status is low. This genetic-nutrient interactive effect is believed to increase the risk for neural tube defects and vascular disease. In this communication, we characterize a second common variant in MTHFR (A1298C), an E to A substitution. Homozygosity was observed in approximately 10% of Canadian individuals. This polymorphism was associated with decreased enzyme activity; homozygotes had approximately 60% of control activity in lymphocytes. Heterozygotes for both the C677T and the A1298C mutation, approximately 15% of individuals, had 50-60% of control activity, a value that was lower than that seen in single heterozygotes for the C677T variant. No individuals were homozygous for both mutations. Additional studies of the A1298C mutation, in the absence and presence of the C677T mutation, are warranted, to adequately address the role of this new genetic variant in complex traits. A silent genetic variant, T1317C, was identified in the same exon. It was relatively infrequent (allele frequency 5%) in our study group, but was quite common in a small sample of African individuals (allele frequency 39%). (C) 1998 Academic Press.