Environmental influence on the worldwide prevalence of a 776C->G variant in the transcobalamin gene (TCN2).
BACKGROUND
A 776C-->G 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 B(12).


OBJECTIVE
To evaluate the worldwide prevalence of this variant and its association with homocysteine plasma level.


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 (Bénin 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 B(12) (<100 pmol/l).


CONCLUSIONS
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.
Guéant
Jean-Louis
JL
Inserm U-724, Cellular and Molecular Pathology in Nutrition, Faculté de Médecine, University Henry Poincaré of Nancy, Vandoeuvre lès Nancy, France. jl.gueant@chu-nancy.fr
Chabi
Nicodème W
NW
Guéant-Rodriguez
Rosa-Maria
RM
Mutchinick
Osvaldo M
OM
Debard
Renée
R
Payet
Corinne
C
Lu
Xiaohong
X
Villaume
Christian
C
Bronowicki
Jean-Pierre
JP
Quadros
Edward V
EV
Sanni
Ambaliou
A
Amouzou
Emile
E
Xia
Bing
B
Chen
Min
M
Anello
Guido
G
Bosco
Paolo
P
Romano
Corrado
C
Arrieta
Heidy R
HR
Sánchez
Beatríz E
BE
Romano
Antonino
A
Herbeth
Bernard
B
Anwar
Wafaa
W
Namour
Fares
F
D000328:Adult; D003596:Cytosine; D004777:Environment; D005787:Gene Frequency / Q000235:genetics*; D005838:Genotype; D006147:Guanine; D006710:Homocysteine / Q000097:blood; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D014155:Transcobalamins / Q000235:genetics*
D014155:Transcobalamins; D006710:Homocysteine; D006147:Guanine; D003596:Cytosine; D042965:Methylenetetrahydrofolate Reductase (NADPH2)