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ORIGINAL RESEARCH COMMUNICATION |
T mutation of the gene encoding methylenetetrahydrofolate reductase in coastal West Africa1,2,3
1 From the Laboratory of Cellular and Molecular Pathology in Nutrition, EMI INSERM 00-14, Vandoeuvre-les-Nancy, France (EKA, CEA, RMR-G, FF, CV, and J-LG); the Laboratory of Biochemistry and Nutrition, Lomé, Togo (EKA); and the Laboratory of Biochemistry and Molecular Biology, Benin (NWC and AS).
Background: Moderate hyperhomocysteinemia is a risk for neural tube defect and neurodegenerative and vascular diseases and has nutritional, metabolic, and genetic determinants. Its prevalence in sub-Saharan Africa remains unknown.
Objective: Our goal was to evaluate the prevalence of hyperhomocysteinemia and the influence of nutritional, metabolic, and genetic determinants in savanna and coastal regions of Togo and Benin.
Design: Volunteers were recruited from coastal (C groups; n = 208) and savanna (S group; n = 68) regions. Vitamin B-12, folate, total homocysteine (tHcy), cystatin C (a marker of glomerular filtration), and inflammatory and nutritional protein markers were measured in plasma, and the methylenetetrahydrofolate reductase (MTHFR) 677C
T and 1298A C polymorphisms and the methionine synthase 2756AG polymorphism were examined in genomic DNA.
Results: Moderate hyperhomocysteinemia (tHcy > 15 µmol/L) was recorded in 62.3% and 29.4% of the subjects from the coast and savanna, respectively (P < 0.0001). A histogram distribution of tHcy in the coastal groups showed a distinct group, C2 (15% of the total group), with tHcy > 28 µmol/L. Folate < 6.75 nmol/L (lower quartile) and MTHFRCT/TT genotype were the 2 main risk factors for moderate hyperhomocysteinemia in the whole population [odds ratios: 5.3 (95% CI: 2.5, 11.2; P < 0.0001) and 4.9 (1.6, 14.8; P = 0.0048), respectively] and in the C2 group [odds ratios: 15.9 (4.5, 56.8; P < 0.0001) and 9.0 (2.3, -35.2; P = 0.0017), respectively]. Cystatin C was another potent risk factor in the C2 group.
Conclusion: A high prevalence of hyperhomocysteinemia in coastal West Africa, related to folate concentrations and the MTHFR 677 T allele, suggests the need to evaluate the influence of hyperhomocysteinemia on disease in this area.
Key Words: Homocysteine • folate • vitamin B-12 • methylenetetrahydrofolate reductase • cystatin C
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