Summary

methylenetetrahydrofolate reductase polymorphism (MTHFRC677T) is an established determinant of homocysteine plasmalevel (t-Hcys) while its association with coronary artery disease(CAD) seems to be more limited. In contrast, the association ofthe substitutions A2756G of methionine synthase (MTR), A66G ofmethionine synthase reductase (MTRR) and C776G of transcobalamin( TCN) to both t-Hcys and CAD needs to be evaluatedfurther.The objective was to evaluate the association of thesepolymorphisms with t-Hcys and CAD in a French population.We investigated the individual and combined effects of thesepolymorphisms and of vitamin B12 and folates with t-Hcys in530 CAD patients and 248 matched healthy controls. t-Hcyswas higher in the CAD group than in controls (11.8 vs 10.4 µ M,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 µ M, P=0.0102 and 12.5 vs 11.0 mM, P=0.0065 respectively).The frequency of MTRR A allele was higher in CADpatients 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 forMTHFR 677T frequency. In multivariate analysis, t-Hcys > medianand MTRR AA genotype were two significant independent predictorsof 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 genotypeis a genetic determinant of moderate hyperhomocysteinemiaassociated with CAD in a French population without vitaminfortification.