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Environmental influence on the world-wide prevalence of a 776C>G variant in the transcobalamin gene (TCN2)
  1. Jean-Louis Guéant (jl.gueant{at}chu-nancy.fr)
  1. INSERM U724, France
    1. Nicodème Chabi (nicodeme.chabi{at}gmail.com)
    1. Université de Cotonou, Benin
      1. Rosa-Maria Guéant-Rodriguez (rm.rodriguez{at}chu-nancy.fr)
      1. INSERM U724, France
        1. Osvaldo Mutchinick (osvaldo{at}servidor.unam.mx)
        1. Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico
          1. Renée Debard (biochbiomol.brab{at}chu-nancy.fr)
          1. INSERM U724, France
            1. Corinne Payet (biochbiomol.brab{at}chu-nancy.fr)
            1. INSERM U724, France
              1. Xiaohong Lu (l_luxiaohong{at}hotmail.com)
              1. INSERM U724, France
                1. Christian Villaume (christian.villaume{at}nancy.inserm.fr)
                1. INSERM U724, France
                  1. Jean-Pierre Bronowicki (jp.bronowicki{at}chu-nancy.fr)
                  1. INSERM U724, France
                    1. Edward Quadros (edward.quadros{at}downstate.edu)
                    1. SUNY-Downstate Medical Center, United States
                      1. Ambaliou Sanni (sanni{at}intnet.bj)
                      1. Univesité de Cotonou, Benin
                        1. Emile Amouzou (kousanta{at}yahoo.fr)
                        1. University of Lomé, Togo
                          1. Bing Xia (bingxia2004{at}yahoo.com.cn)
                          1. Wuhan University Medical School, China
                            1. Min Chen (chenmin8106{at}yahoo.com.cn)
                            1. Wuhan University Medical School, China
                              1. Guido Anello (anello{at}oasi.en.it)
                              1. IRCCS, Oasi Maria S.S, Italy
                                1. Paolo Bosco (pbosco{at}oasi.en.it)
                                1. IRCCS, Oasi Maria S.S, Italy
                                  1. Corrado Romano (cromano{at}oasi.en.it)
                                  1. IRCCS, Oasi Maria S.S, Italy
                                    1. Heidy Arrieta (heidy{at}servidor.unam.mx)
                                    1. Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico
                                      1. Beatriz Sánchez (beatriz{at}servidor.unam.mx)
                                      1. Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico
                                        1. Antonino Romano (columbus.romano{at}linet.it)
                                        1. UCSC, CI Colombus Roma, Italy
                                          1. Bernard Herbeth (bernard.herbeth{at}nancy.inserm.fr)
                                          1. INSERM U525, France
                                            1. Wafaa Anwar
                                            1. INSERM U724, France
                                              1. Fares Namour (b.namour{at}chu-nancy.fr)
                                              1. INSERM U724, France

                                                Abstract

                                                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 world-wide 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 subjects with severe malaria. Results: The frequencies of 776G allele were the highest in China (0.607 [95% confidence interval:0.554-0.659]), low in West Africa (Benin and Togo, 0.178 [0.154-0.206]) and intermediate in France (0.445 [0.408-0.481]), Italy (0.352 [0.299-0.409]), Marocco (0.370 [0.300-0.447]) and Mexico (0.374 [0.392-0.41.9]). The 776GG genotype was more frequent in Afro-Americans from New York (16.7 [8.4-30.7]) and in Afro-African patients with severe malaria (6.0% [95%CI: 3.7-9.6]) than in healthy Afro-African volunteers (p=0.0004 and p=0.0329, respectively), while no difference was observed for MTHFR 677TT and 677T allele. A disequilibrium of TCN2 genotype distribution was recorded in the patients with severe malaria, with a 2-fold higher GG genotypes 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: Our results suggest therefore that, 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 being malaria.

                                                • Transcobalamin
                                                • homocysteine
                                                • malaria
                                                • nutrigenetics

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