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ORIGINAL RESEARCH COMMUNICATION |
1 From INSERM U-724, Cellular and Molecular Pathology in Nutrition, Faculté de Médecine, University Henry Poincaré of Nancy, Vandoeuvre lès Nancy, France (R-MG-R, J-LG, RD, ST, LXH, J-PB, and FN); the Laboratory of Biochemistry and Nutrition, Lomé, Togo (NWC and AS); the IRCCS, Oasi Maria SS–Institute for Research on Mental Retardation, Troina, Italy (GA, PB, and CR); the Laboratory of Biochemistry and Molecular Biology, University of Cotonou, Cotonou, Bénin (EA); the Department of Genetics, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico(HRA, BES, and OMM); the Department of Internal Medicine and Geriatrics, Universitá Cattolica del Sacro Cuore, Complesso Integrato Columbus, Rome, Italy (AR); the Preventive Health Care Center and INSERM U525, Nancy, France (BH); and the Department of Physiology and Nutrition, University of Burgundy, Dijon, France (J-CG)
Background: Methylenetetrahydrofolate reductase (MTHFR) 677C
T polymorphism is heterogeneously distributed worldwide, with the highest and lowest frequencies of the T allele in Mexico and Africa, respectively, and a south-to-north gradient in Europe. Distribution of MTHFR 1298AC is less well known. It has been hypothesized that 677T frequency could result in part from gene-nutrient interactions.
Objective: The objective was to compare the association of 677T and 1298C alleles with plasma concentrations of homocysteine, folate, and vitamin B-12 in geographical areas with contrasting 677T allele frequencies.
Design: Healthy young adults (n = 1277) were recruited in Mexico City, the West African countries of Bénin and Togo, France, and Sicily (Italy). Homocysteine, folate, and vitamin B-12 were measured in plasma, and MTHFR polymorphisms were measured in genomic DNA.
Results: Mexico City and Sicily reported the highest and Bénin and Togo reported the lowest plasma concentrations of folate. Mexico City had the highest 677T allele prevalence and the lowest influence of 677TT genotype on homocysteine, whereas the opposite was observed in Africa. The prevalence of the 1298C allele was lowest in the Mexicans and Africans and highest in the French. The percentage of the 677T genotype was significantly associated with the folate concentrations in 677CC carriers in a univariate analysis (R = 0.976; 95% CI: 0.797, 0.996; P < 0.0002) and in a multiple regression model that included homocysteine, vitamin B-12, and age (P = 0.0002).
Conclusion: Our data agree with the hypothesis of a gene-nutrient interaction between MTHFR 677CT polymorphism and folate status that may confer a selective advantage of TT-homozygous genotype when dietary intake of folate is adequate, at least in the areas studied.
Key Words: Methylenetetrahydrofolate reductase • polymorphism • folate • homocysteine • vitamin B-12
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