Aléssio Ana C M, Höehr Nelci F, Siqueira Lúcia H, Bydlowski Sérgio P, Annichino-Bizzacchi Joyce M
Hematology-Hemotherapy Center, Faculty of Medical Sciences, State University of Campinas (UNICAMP), Campinas, SP, Brazil.
Thromb Res. 2007;119(5):571-7. doi: 10.1016/j.thromres.2006.05.009. Epub 2006 Jul 3.
One of the etiologies of hyperhomocysteinemia is decreased vitamin B(12). Genetic variation in the transcobalamin II gene, the transporter of vitamin B(12) to the cells, may produce altered homocysteine levels. We determined transcobalamin II C776G polymorphism, homocysteine, folate and vitamin B(12) levels and analyzed the interactive effect with the methylenetetrahydrofolate reductase C677T and A1298C and methionine synthase reductase A66G polymorphisms in 207 healthy Brazilian children. The prevalence of GG genotype of transcobalamin II C776G polymorphism in this Brazilian population, a highly miscigeneous population was 12.5% and the statistical analysis showed that this population is in Hardy-Weinberg equilibrium, it could be considered representative of the general population. We observed a significant increase in homocysteine in the 776GG vs. 776CC genotype, corroborating the influence of age as a determinant of homocysteine in relation to this polymorphism. When we analyzed vitamin B(12) and its relationship with the C776G polymorphism, we found no significant differences. Only 776CG/66AA or 776GG/66AG genotypes presented a significant increase in homocysteine when compared with other groups. In the multivariate analysis, transcobalamin II C776G (CC/CG vs. GG), methylenetetrahydrofolate reductase C677T (CC/CT vs. TT), folate, gender and age presented statistical significance in relation to the homocysteine. These can be considered independent risk factors for hyperhomocysteinemia in this children group. Our results, if confirmed in other populations, highlight the necessity for investigation of the transcobalamin II C776G polymorphism in the research for hyperhomocysteinemia risk factors.
高同型半胱氨酸血症的病因之一是维生素B12缺乏。维生素B12向细胞转运的转钴胺素II基因的遗传变异可能会改变同型半胱氨酸水平。我们测定了207名健康巴西儿童的转钴胺素II C776G多态性、同型半胱氨酸、叶酸和维生素B12水平，并分析了其与亚甲基四氢叶酸还原酶C677T和A1298C以及甲硫氨酸合成酶还原酶A66G多态性的交互作用。在这个高度混杂的巴西人群中，转钴胺素II C776G多态性的GG基因型患病率为12.5%，统计分析表明该人群处于哈迪-温伯格平衡，可以被认为是一般人群的代表。我们观察到776GG基因型与776CC基因型相比，同型半胱氨酸显著升高，这证实了年龄作为该多态性相关同型半胱氨酸决定因素的影响。当我们分析维生素B12及其与C776G多态性的关系时，未发现显著差异。与其他组相比，只有776CG/66AA或776GG/66AG基因型的同型半胱氨酸显著升高。在多变量分析中，转钴胺素II C776G（CC/CG与GG）、亚甲基四氢叶酸还原酶C677T（CC/CT与TT）、叶酸、性别和年龄与同型半胱氨酸具有统计学意义。这些可被视为该儿童群体高同型半胱氨酸血症的独立危险因素。如果在其他人群中得到证实，我们的结果突出了在高同型半胱氨酸血症危险因素研究中调查转钴胺素II C776G多态性的必要性。
