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European Heart Journal 1999 20(8):584-592; doi:10.1053/euhj.1998.1340
Copyright © 1999 by the European Society of Cardiology.
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The TT genotype of the methylenetetrahydrofolate reductase C677T gene polymorphism is associated with the extent of coronary atherosclerosis in patients at high risk for coronary artery disease

A. Gardemanna,f1, H. Weidemanna, M. Philippa, N. Katza, H. Tillmannsb, F. Wilhelm Hehrleinc and W. Haberboschd

a Institut für Klinische Chemie und Pathobiochemie, Giessen, Germany
b Abteilung Kardiologie und Angiologie, Giessen, Germany
c Klinik für Herz- und Gefäßchirurgie der Justus-Liebig-Universität Giessen, Giessen, Germany
d Max-Planck-Institut für Experimentelle und Klinische Forschung, Kerckhoff-Klinik, Bad Nauheim, Germany

revised September 17, 1998; accepted September 30, 1998

Abstract

Background

There are conflicting results on the relationship of N5,N10-methylenetetrahydrofolate reductase C677T gene variation in coronary artery disease and myocardial infarction.

Methods and Results

We analysed this gene variation in 2453 male Caucasians whose coronary anatomy was defined by coronary angiography. In the total sample, the C677T gene polymorphism was not associated with the presence or the extent of coronary artery disease (defined by the degree of vessel disease or by the coronary heart disease score according to Gensini). However, after excluding individuals with low risk profiles, an association between the C677T TT genotype and the Gensini score was found. This observation applies only to individuals (i) with high glucose levels, (ii) with low apolipoprotein Al/apolipoprotein B ratios, (iii) with low apolipoprotein Al/apolipoprotein B ratios and high lipoprotein (a) levels and (iv) with low apolipoprotein Al/apolipoprotein B ratios and high glucose concentrations. In patients with high glucose levels, the paraoxonase 191 A/B gene variation presupposed whether differences in Gensini scores between C677T C allele carriers and TT homozygotes became apparent, since only in paraoxonase 191 AA homoxygotes, but not in paraoxonase 191 B allele carriers, did C677T TT homozygotes have clearly higher Gensini scores than C allele carriers (two-way interaction;P=0·013). The MTHFR C677T gene polymorphism was not associated with non-fatal myocardial infarction.

Conclusion

The present study extends previous observations by the finding that carriers of the N5,N10-methylenetetrahydrofolate reductase C677T TT genotype with various coronary high risk profiles had clearly higher coronary heart disease scores than individuals with at least one C677T C allele.

Key Words: Homocysteine metabolism, coronary artery disease, myocardial infarction, coronary risk factors

f1 Correspondence: Andreas Gardemann, Institut für Klinische Chemie und Pathobiochemie, Klinikum der Justus-Liebig-Universität Gießen, Gaffky-Strasse 11, 35392 Gießen, Germany.

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