Déterminants génétiques et nutritionnels de l'homocystéine : études de populations et association avec les maladies cardiovasculaires

Abstract : We have compared the association of MTHFR 677T and 1298C alleles with folate, in geographical areas with contrasting allele frequencies. Mexico and Sieily were the two areas giving the highest and West Africa the lowest level of folate. Mexico had the highest 677T allele prevalence and the lowest influence of 677TT genotype on Homocysteine (Hey), the opposite being observed in Africa. Our data agreed with the hypothesis of a gene-nutrient interaction between 677->T polymorphism and folate. Hey is a risk factor for coronary artery disease (CAD) and acute congestive heart failure. Hey is a risk factor coronary artery disease (CAD) and acute congestive heart failure. We have evaluated its association with left ventricular systolic dysfunction in 560 patients referred for diagnostic coronary angiography. Hey was higher in the 138 patients having a left ventricular ejection fraction (LVEF)<40% (P<0,0001). It was correlated with LVEF and NT-pro-BNP in univariate and multiple regression (P<0.0001 and P=0.0073, respectively). Its association with LVEF was independent from that with CAD. Association with LVEF was independent from that with CAD. Association of MTHFR C677T with CAD seems to be limited while that withMTR A2756G, MTRR A66G and TCN C776G needs to be evaluated further. We investigated these polymorphisms in 530 CAD patients and 248 matched controls. Hey was higher in CAD group than in controls (P<0.0001) and carriers of MTRR AA AND MTHFR 677 TT (P=0,0102 and P=0,0065, respectively). The frequency of MTRR A allele was higher in patients than in controls (P=0,0081). In multivariate analysis, Hey>median and MTRR AA genotype were two independant predictors of CAD. In contrast to NORTH Europe studies, MTRR AA is a genetic determinant of Hey and CAD in a French population without vitamin fortification.
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http://docnum.univ-lorraine.fr/prive/SCD_T_2005_0221_GUEANT_RODRIGUEZ.pdf
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Rosa-Maria Guéant-Rodriguez. Déterminants génétiques et nutritionnels de l'homocystéine : études de populations et association avec les maladies cardiovasculaires. Sciences agricoles. Université Henri Poincaré - Nancy 1, 2005. Français. ⟨NNT : 2005NAN11312⟩. ⟨tel-01746978⟩

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