Aléssio Ana Claudia M, Annichino-Bizzacchi Joyce M, Bydlowski Sergio P, Eberlin Marcos N, Vellasco Adriana P, Höehr Nelci Fenalti
Hematology-Hemotherapy Center, Faculty of Medical Sciences, State University of Campinas (UNICAMP), Campinas, SP, Brazil.
Am J Med Genet A. 2004 Jul 30;128A(3):256-60. doi: 10.1002/ajmg.a.30108.
Hyperhomocysteinemia is a risk factor for thrombosis, and methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR) polymorphisms, folate, and B12 levels could contribute to plasma homocysteine (Hcy) variation. Although well established in adults, few studies have been performed in childhood. In this study, we investigated association of polymorphisms C677T and A1298C in the MTHFR gene and A66G in the MTRR gene with Hcy levels in children. These polymorphisms, as well as Hcy, folate, and vitamin B12 levels were investigated in 220 normal children with ages ranging from 1 to 8 years. Plasma Hcy, folate, and vitamin B12 levels were normal in all children. None of the polymorphisms could be considered an independent risk factor for hyperhomocysteinemia during childhood. The median Hcy levels in 37 children (17%) doubly heterozygous for C677T and A1298C mutations in the MTHFR gene were not different from the other genotypes. However, the association of the different genotypes with Hcy, folate, and vitamin B12 levels demonstrated significant P-values. The folate levels demonstrated a statistically significant decrease (P = 0.0477) from the C677T mutation in the MTHFR gene (TT genotype) when compared to the other groups. Folate was the only independent risk factor for hyperhomocysteinemia. Thus, monitoring the concentrations of folate would be more helpful for evaluating hyperhomocysteinemia and for preventing cardiovascular disease.
高同型半胱氨酸血症是血栓形成的一个危险因素，亚甲基四氢叶酸还原酶（MTHFR）和甲硫氨酸合成酶还原酶（MTRR）基因多态性、叶酸及维生素B12水平可能导致血浆同型半胱氨酸（Hcy）水平变化。虽然在成年人中已有充分研究，但在儿童中进行的研究较少。在本研究中，我们调查了MTHFR基因的C677T和A1298C多态性以及MTRR基因的A66G多态性与儿童Hcy水平的相关性。对220名年龄在1至8岁的正常儿童进行了这些多态性以及Hcy、叶酸和维生素B12水平的检测。所有儿童的血浆Hcy、叶酸和维生素B12水平均正常。在儿童期，没有一种多态性可被视为高同型半胱氨酸血症的独立危险因素。37名（17%）MTHFR基因C677T和A1298C突变双重杂合子儿童的Hcy水平中位数与其他基因型儿童无差异。然而，不同基因型与Hcy、叶酸和维生素B12水平的相关性显示出显著的P值。与其他组相比，MTHFR基因C677T突变（TT基因型）儿童的叶酸水平有统计学意义的下降（P = 0.0477）。叶酸是高同型半胱氨酸血症的唯一独立危险因素。因此，监测叶酸浓度对评估高同型半胱氨酸血症和预防心血管疾病更有帮助。
