Correlation between C677T MTHFR gene polymorphism, plasma homocysteine levels and the incidence of CAD

被引：27
作者：
Nakai K. [1 ,4 ]
Itoh C. [1 ]
Nakai K. [1 ,4 ]
Habano W. [2 ]
Gurwitz D. [3 ]
机构：
[1] Laboratory Medicine, Iwate Medical University, Morioka
[2] DNA Laboratory, Iwate Medical University
[3] National Laboratory for the Genetics of Israeli Populations, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv
[4] Laboratory Medicine, Iwate Medical University, Morioka, 020-8505
来源：
American Journal of Cardiovascular Drugs | 2001年 / 1卷 / 5期
关键词：
Homocysteine; Hyperhomocysteinemia; C677T MTHFR; MTHFR Gene; Plasma Homocysteine Level;
D O I：
10.2165/00129784-200101050-00005
中图分类号：
学科分类号：
摘要：
The lesions of coronary atherosclerosis represent the result of a complex, multicellular, inflammatoryhealing response in the coronary arterial wall. In vivo and in vitro cellular and molecular studies have suggested a role for tissue homocysteine in endothelial cell injury and adverse extra-cellular matrix remodeling. Gene polymorphisms in relation with numerous risk factors might increase the incidence of coronary artery disease (CAD). In this review we have focused on the correlations between plasma homocysteine levels, the incidence of cardiovascular disease and the cytosine-to-thymidine substitution at nucleotide 677 (C677T) of the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene, coding for a key enzyme in methionine-homocysteine metabolism. The role of the C677T MTHFR gene polymorphism in the causation of CAD is controversial. We reviewed 12 recent case-control studies comprising 5370 genotyped patients with CAD and 4961 genotyped participants without CAD. There was no significant difference between those with and without CAD in the frequency of the C677T polymorphism (34.9 vs 33.6%). The frequency of homozygous C677T polymorphism in these groups was 10.9 versus 12.8%, respectively, although there were some ethnic differences in the C677T MTHFR polymorphism. In the analysis of the 12 studies, the odds ratio of CAD associated with the TT genotype (homozygous C677T polymorphism) was 1.18. Only slightly higher plasma homocysteine levels were observed in participants with the val/val (TT) genotype (14.4 ±?2.9 μmol/L in TT genotype vs 11.1 ±?1.9 and 11.9 ±?2 μmol/L in CC and CT genotype, respectively). In addition, the relation between homocysteine increase after methionine loading and MTHFR genotypes is also controversial. However, hyperhomocysteinemia because of the C677T MTHFR allele may be corrected with oral folic acid therapy. Further investigations on the relationships between MTHFR genotypes and the incidence of CAD should be based on larger samples, paying attention to the differences between various ethnic populations. Individual therapeutic strategies based on single nucleotide polymorphism may become increasingly important for preventive treatment against polygenic CAD. © Adis International Limited All rights reserved.
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页码：353 / 361
页数：8
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