Association of MTRR A66G polymorphism (but not of MTHFR C677T and A1298C, MTR A2756G, TCN C776G) with homocysteine and coronary artery disease in the French population

Rosa-Maria Guéant-Rodriguez; Yves Juilliére; Mirande Candito; Charles E. Adjalla; Pierre Gibelin; Bernard Herbeth; Emmanuel Van Obberghen; Jean-Louis Guéant

doi:10.1160/TH05-04-0262

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 2005; 94(03): 510-515
DOI: 10.1160/TH05-04-0262

Blood Coagulation, Fibrinolysis and Cellular Haemostasis

Schattauer GmbH

Association of MTRR A66G polymorphism (but not of MTHFR C677T and A1298C, MTR A2756G, TCN C776G) with homocysteine and coronary artery disease in the French population

Authors

Rosa-Maria Guéant-Rodriguez

¹INSERM U-724, Laboratory of Cellular and Molecular Pathology in Nutrition, Faculty of Medicine, Vandoeuvre-les-Nancy Cedex, France

²Department of Cardiology, University Hospital Center of Nancy, France
Yves Juilliére

¹INSERM U-724, Laboratory of Cellular and Molecular Pathology in Nutrition, Faculty of Medicine, Vandoeuvre-les-Nancy Cedex, France

²Department of Cardiology, University Hospital Center of Nancy, France
Mirande Candito

³Departments of Biochemistry and Cardiology, University Hospital Center of Nice, France
Charles E. Adjalla

¹INSERM U-724, Laboratory of Cellular and Molecular Pathology in Nutrition, Faculty of Medicine, Vandoeuvre-les-Nancy Cedex, France
Pierre Gibelin

³Departments of Biochemistry and Cardiology, University Hospital Center of Nice, France
Bernard Herbeth

⁴Centre de Médecine Préventive de Nancy, Vandoeuvre-les-Nancy, France
Emmanuel Van Obberghen

³Departments of Biochemistry and Cardiology, University Hospital Center of Nice, France
Jean-Louis Guéant

¹INSERM U-724, Laboratory of Cellular and Molecular Pathology in Nutrition, Faculty of Medicine, Vandoeuvre-les-Nancy Cedex, France

Abstract

Summary

methylenetetrahydrofolate reductase polymorphism (MTHFR C677T) is an established determinant of homocysteine plasma level (t-Hcys) while its association with coronary artery disease (CAD) seems to be more limited. In contrast, the association of the substitutions A2756G of methionine synthase (MTR), A66G of methionine synthase reductase (MTRR) and C776G of transcobalamin (TCN) to both t-Hcys and CAD needs to be evaluated further. The objective was to evaluate the association of these polymorphisms with t-Hcys and CAD in a French population. We investigated the individual and combined effects of these polymorphisms and of vitamin B12 and folates with t-Hcys in 530 CAD patients and 248 matched healthy controls. t-Hcys was higher in the CAD group than in controls (11.8 vs 10.4 μM, P<0.0001) and in carriers of MTRR AA and MTHFR 677TT than in those carrying the most frequent allele of both polymorphisms (13.8 vs 11.4 μM, P=0.0102 and 12.5 vs 11.0 mM, P=0.0065 respectively). The frequency of MTRR A allele was higher in CAD patients than in controls (0.48 [95% CI: 0.44-0.52] vs 0.38 [95% CI: 0.32-0.44], P=0.0081) while no difference was observed for MTHFR 677T frequency. In multivariate analysis, t-Hcys > median and MTRR AA genotype were two significant independent predictors of CAD with respective odds ratios of 3.1 (95 % CI: 1.8-5.1, P<0.0001) and 4.5 (95% CI: 1.5-13.1, P=0.0051). In conclusion, in contrast to North Europe studies, MTRR AA genotype is a genetic determinant of moderate hyperhomocysteinemia associated with CAD in a French population without vitamin fortification.

Keywords

Coronary artery disease - folate - homocysteine - methionine synthase reductase - transcobalamin - vitamin B12

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Referenzen

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