title: Low frequency of mutated methylenetetrahydrofolate reductase 677C-->T and 1298A-->C genetics single nucleotide polymorphisms (SNPs) in Sub-Saharan populations.
abstract: 5,10-Methylenetetrahydrofolate reductase (MTHFR) and methionine synthase (MTR) are two of the key enzymes in the folate/vitamin B12-dependent remethylation of homocysteine to methionine. The frequencies of MTHFR single nucleotide polymorphisms (SNPs), 677C-->T, 1298A-->C, 1317T-->C and of MTR, 2756A-->G, have been widely studied in Caucasians, but they have never been reported simultaneously in a large population from Sub-Saharan Africa. Presently, we report the prevalence of these SNPs and their relationship to homocysteine in 240 subjects recruited in West Africa. The frequencies of the mutant genotypes 677TT (0.8%) and 1298CC (2%) were lower than that usually observed in Caucasians, while the frequency of the mutant 1317CC was higher (16%). We formed a systematic association of the mutated MTHFR 677C-->T SNP with a 1298A/1317T common haplotype. The MTHFR mutant genotype 677TT was associated with an intermediate hyperhomocysteinemia (92.4 +/- 6.0 micromol/l) higher than that described in Caucasians. The 2756A-->G SNP in the MTR was similarly distributed in Africans compared to Caucasians. In conclusion, the MTHFR 677TTor 1298CC genotypes are much rarer in Africans than in Caucasians. The 677TT low frequency may be related to the high effect of this mutation on homocysteine metabolism in the environmental conditions of this African region.
authors.affiliation: Laboratory of Cellular and Molecular Pathology in Nutrition, INSERM 00-14, Faculty of Medicine, Vandoeuvre lès Nancy, France.
authors.forename: Charles E
authors.initials: CE
authors.lastname: Adjalla
authors.forename: Emile K
authors.initials: EK
authors.lastname: Amouzou
authors.forename: Ambaliou
authors.initials: A
authors.lastname: Sanni
authors.forename: Idrissia
authors.initials: I
authors.lastname: Abdelmouttaleb
authors.forename: Nicodème W
authors.initials: NW
authors.lastname: Chabi
authors.forename: Fares
authors.initials: F
authors.lastname: Namour
authors.forename: Batoma
authors.initials: B
authors.lastname: Soussou
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Guéant
mesh_terms: D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase / Q000235:genetics; D000328:Adult; D017954:Africa South of the Sahara; D004247:DNA / Q000097:blood / Q000235:genetics / Q000302:isolation & purification; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006710:Homocysteine / Q000097:blood; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D017354:Point Mutation / Q000235:genetics; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*
chemical_list: D006710:Homocysteine; D004247:DNA; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase