||Background: A 776CRG variant (dbSNP ID: rs1801198) in the transcobalamin gene (TCN2; MIM#
275350) decreases the cellular and plasma concentration of transcobalamin and thereby influences the
cellular availability of vitamin B12.
Objective: To evaluate the worldwide prevalence of this variant and its association with homocysteine plasma
Methods: The study was performed in 1433 apparently healthy subjects, including Afro-Americans and Afro-
Africans and in 251 Afro-Africans participants with severe malaria.
Results: The frequencies of the 776G allele were the highest in China (0.607; 95% CI 0.554 to 0.659), low in
West Africa (Be´nin and Togo, 0.178; 0.154 to 0.206), and intermediate in France (0.445; 0.408 to 0.481),
Italy (0.352; 0.299 to 0.409), Morocco (0.370; 0.300 to 0.447) and Mexico (0.374; 0.392 to 0.419). The
776G genotype was more frequent in Afro-Americans from New York (16.7; 8.4 to 30.7) and in Afro-
African patients with severe malaria (6.0%; 95% CI 3.7 to 9.6) than in healthy Afro-African volunteers
(p = 0.0004 and p = 0.033, respectively), while no difference was observed for MTHFR 677TT and 677T
alleles. A disequilibrium of TCN2 genotype distribution was recorded in patients with severe malaria, with a
twofold higher GG genotype than expected (p = 0.010). An association between the TCN2 polymorphism
and homocysteine was observed only in Mexico and France, the two countries with the highest rate of low
plasma concentration of vitamin B12 (,100 pmol/l).
Conclusion: Given the dramatic heterogeneity of the 776G allele frequency worldwide, this polymorphism
may be prone to a selective pressure or confers an evolutionary advantage in confronting environmental
factors, one of which is malaria.