Prevalence of methylenetetrahydrofolate reductase 677T and 1298C alleles and folate status: a comparative study in Mexican, West African, and European populations.
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 1298A-->C 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.


METHODS
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).


CONCLUSIONS
Our data agree with the hypothesis of a gene-nutrient interaction between MTHFR 677C-->T 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.
Guéant-Rodriguez
Rosa-Maria
RM
INSERM U-724, Cellular and Molecular Pathology in Nutrition, Faculté de Médecine, University Henry Poincaré of Nancy, Vandoeuvre lès Nancy, France.
Guéant
Jean-Louis
JL
Debard
Renée
R
Thirion
Sylvie
S
Hong
Lu Xiao
LX
Bronowicki
Jean-Pierre
JP
Namour
Farès
F
Chabi
Nicodème W
NW
Sanni
Ambaliou
A
Anello
Guido
G
Bosco
Paolo
P
Romano
Corrado
C
Amouzou
Emile
E
Arrieta
Heidy R
HR
Sánchez
Beatríz E
BE
Romano
Antonino
A
Herbeth
Bernard
B
Guilland
Jean-Claude
JC
Mutchinick
Osvaldo M
OM
D000293:Adolescent; D000328:Adult; D000354:Africa, Western; D000483:Alleles; D005060:Europe; D005260:Female; D005492:Folic Acid / Q000097:blood*; D005787:Gene Frequency; D005838:Genotype; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008800:Mexico; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012044:Regression Analysis; D014805:Vitamin B 12 / Q000097:blood*
D006710:Homocysteine; D005492:Folic Acid; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D014805:Vitamin B 12