Guéant-Rodriguez R M, Rendeli C, Namour B, Venuti L, Romano A, Anello G, Bosco P, Debard R, Gérard P, Viola M, Salvaggio E, Guéant J L
Cellular and Molecular Pathology in Nutrition, EMI - INSERM 0014 - URM IFREMER 20, Faculty of Medicine BP 184, 54500, Vandoeuvre lès Nancy, France.
Neurosci Lett. 2003 Jul 3;344(3):189-92. doi: 10.1016/s0304-3940(03)00468-3.
The pathogenic mechanism of neural tube defects may involve genetic polymorphisms and nutritional factors related to homocysteine metabolism. We evaluated the association of polymorphisms of three genes affecting vitamin B12-dependent remethylation of homocysteine, transcobalamin (TC), methionine synthase (MTR) and MTR reductase (MTRR), combined or not with methylenetetrahydrofolate reductase (MTHFR), with the risk of having neural tube defect in 40 children with spina bifida and 58 matched controls from South Italy. MTR 2756 AG/GG, TC 777 CG/GG /MTHFR 677 CC and MTRR 66 GG /MTHFR 677 CC genotypes increased the risk with odds ratios of 2.6 (P=0.046), 2.4 (P=0.028) and 4.5 (P=0.023), respectively. In contrast, MTHFR 677 TT was protective (odds ratio=0.11, P=0.009). In conclusion, genetic determinants affecting the cellular availability or MTRR-dependent reduction of B12 may increase the risk of spina bifida.
神经管缺陷的致病机制可能涉及与同型半胱氨酸代谢相关的基因多态性和营养因素。我们评估了影响同型半胱氨酸维生素B12依赖性再甲基化的三个基因，即转钴胺素（TC）、甲硫氨酸合成酶（MTR）和MTR还原酶（MTRR），无论是否与亚甲基四氢叶酸还原酶（MTHFR）联合，其基因多态性与来自意大利南部的40名脊柱裂患儿和58名匹配对照患神经管缺陷风险之间的关联。MTR 2756 AG/GG、TC 777 CG/GG /MTHFR 677 CC以及MTRR 66 GG /MTHFR 677 CC基因型使风险增加，比值比分别为2.6（P = 0.046）、2.4（P = 0.028）和4.5（P = 0.023）。相反，MTHFR 677 TT具有保护作用（比值比 = 0.11，P = 0.009）。总之，影响细胞内维生素B12可用性或MTRR依赖性还原的遗传决定因素可能会增加脊柱裂的风险。
