Association of MTRRA66G polymorphism (but not of MTHFR C677T and A1298C, MTRA2756G, TCN C776G) with homocysteine and coronary artery disease in the French population.
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 microM, P < 0.0001) and in carriers of MTRRAA and MTHFR 677TT than in those carrying the most frequent allele of both polymorphisms (13.8 vs 11.4 microM, 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 MTRRAA 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, MTRRAA genotype is a genetic determinant of moderate hyperhomocysteinemia associated with CAD in a French population without vitamin fortification.
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CHEMICAL CHEMICAL CHEMICAL GENE-Y GENE-Y GENE-Y GENE-Y GENE-Y GENE-N GENE-Y CHEMICAL GENE-Y GENE-N GENE-Y GENE-Y GENE-N GENE-N GENE-N GENE-Y GENE-N GENE-Y CHEMICAL GENE-Y GENE-Y GENE-N GENE-Y GENE-N GENE-N GENE-Y GENE-N GENE-N GENE-N CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL
Hcys homocysteine homocysteine Methylenetetrahydrofolate reductase MTRR MTHFR MTRR MTRR A2756G methionine synthase Methylenetetrahydrofolate MTR A66G methionine synthase reductase MTRR C776G transcobalamin TCN MTHFR C677T MTRR Hcys MTHFR MTRR A66G MTHFR C677T A1298C MTR A2756G TCN C776G Hcys methionine methionine Hcys Hcys vitamin B12 folates