High prevalence of hyperhomocysteinemia related to folate deficiency and the 677C3T mutation of the gene encoding methylenetetrahydrofolate reductase in coastal West Africa

Abstract

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) 677C3T and 1298A3C polymorphisms and the methionine synthase 2756A3G polymorphism were examined in genomic DNA. Results: Moderate hyperhomocysteinemia (tHcy  15
mol/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
mol/L. Folate  6.75 nmol/L (lower quartile) and MTHFR CT/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:Ahigh 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.