Identification of six methylenetetrahydrofolate reductase ( MTHFR) genotypes resulting from common polymorphisms: impact on plasma homocysteine levels and development of coronary artery disease

Although three common MTHFR polymorphisms (C 677T, A 1298C, T 1317C) have been reported, only polymorphism C 677T has been investigated intensively as a risk factor for coronary artery disease (CAD). We investigated polymorphism frequencies, allelic associations and the effect of the resulting MTHFR...

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Published in:Atherosclerosis 2001-02, Vol.154 (3), p.651-658
Main Authors: Meisel, Christian, Cascorbi, Ingolf, Gerloff, Thomas, Stangl, Verena, Laule, Michael, Müller, Joachim M, Wernecke, Klaus D, Baumann, Gert, Roots, Ivar, Stangl, Karl
Format: Article
Language:English
Subjects:
Acute coronary syndrome
Atherogenic risk factors
Coronary artery disease
Coronary Disease - genetics
Gene Frequency
Genotype
Homocysteine
Homocysteine - blood
Humans
Methylenetetrahydrofolate Reductase (NADPH2)
Methylenetetrahydrofolate reductase polymorphism
Oxidoreductases Acting on CH-NH Group Donors - genetics
Polymorphism, Genetic - physiology
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Summary:Although three common MTHFR polymorphisms (C 677T, A 1298C, T 1317C) have been reported, only polymorphism C 677T has been investigated intensively as a risk factor for coronary artery disease (CAD). We investigated polymorphism frequencies, allelic associations and the effect of the resulting MTHFR genotypes on total plasma homocysteine (tHcy) levels and on coronary risk in a case-control study with 1000 angiographically confirmed Middle-European CAD patients and 1000 matched controls. Three out of four theoretically possible MTHFR haplotypes were detected: *1 (677C, 1298A), *2 (677T, 1298A), and *3 (677C, 1298C). The frequencies were *1: 36.4 and 34.4%; *2: 30.8 and 32.3%; and *3: 32.8 and 33.3%, in cases and controls, respectively. Only one patient was heterozygous for 1317C. None of the six resulting genotypes showed significant influence on tHcy levels. Moreover, there was no significant association with CAD risk or with disease severity or early disease manifestation. In the subgroup presenting with acute coronary syndromes, MTHFR genotypes *2/*3 and *3/*3 were surprisingly underrepresented (relative risk of *3/*3, 0.40; 95% confidence interval 0.20–0.79, P=0.009). We conclude from our genotype-based analysis that, in this well-fed Middle-European population, the observed common allelic variants of the MTHFR gene have no significant influence on tHcy levels or on the chronic process of CAD development.
ISSN:0021-9150
1879-1484
DOI:10.1016/S0021-9150(00)00679-1