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Environmental influence on the worldwide prevalence of a 776C→G variant in the transcobalamin gene (TCN2)
  1. Jean-Louis Guéant1,
  2. Nicodème W Chabi4,
  3. Rosa-Maria Guéant-Rodriguez1,
  4. Osvaldo M Mutchinick2,
  5. Renée Debard1,
  6. Corinne Payet1,
  7. Xiaohong Lu1,
  8. Christian Villaume1,
  9. Jean-Pierre Bronowicki1,
  10. Edward V Quadros3,
  11. Ambaliou Sanni4,
  12. Emile Amouzou5,
  13. Bing Xia6,
  14. Min Chen6,
  15. Guido Anello7,
  16. Paolo Bosco7,
  17. Corrado Romano7,
  18. Heidy R Arrieta2,
  19. Beatríz E Sánchez2,
  20. Antonino Romano8,
  21. Bernard Herbeth9,
  22. Wafaa Anwar10,
  23. Fares Namour1
  1. 1Inserm U-724, Cellular and Molecular Pathology in Nutrition, Faculté de Médecine, University Henry Poincaré of Nancy, Vandoeuvre lès Nancy, France
  2. 2Departamento de Genética, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico city, México
  3. 3Department of Biochemistry, SUNY-Downstate Medical Center, Brooklyn, New York, USA
  4. 4Laboratory of Biochemistry and Molecular Biology, Université de Cotonou, Bénin
  5. 5Laboratory of Biochemistry and Nutrition, Lomé, Togo
  6. 6Department of Internal Medicine and Geriatrics, Zhongnan Hospital and Research Center of Digestive Diseases, Wuhan University Medical School, Wuhan, PR China
  7. 7IRCCS, Oasi Maria SS–Institute for Research on Mental Retardation, Troina (EN), Italy
  8. 8Department of Internal Medicine and Geriatrics, UCSC, CI Columbus, Roma, Italy
  9. 9Inserm U525, Nancy, France
  10. 10Département de Biologie, Faculté de Médecine, Casablanca, Morocco
  1. Correspondence to:
 Professor J-L Guéant
 Inserm U-724, Cellular and Molecular Pathology in Nutrition, Faculté de Médecine, University Henry Poincaré of Nancy, BP 184, 54500, Vandoeuvre lès Nancy, France; jl.gueant{at}


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 B12.

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 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.

  • MTHFR, methylenetetrahydrofolate reductase

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  • Published Online First 12 January 2007

  • Competing interests: None.