Departamento de Biologia Molecular, Faculdade de Medicina de São José do Rio Preto (FAMERP), Unidade de Pesquisa em Genética e Biologia Molecular (UPGEM), Av. Brigadeiro Faria Lima, n.o 5416-Bloco U-6, São José do Rio Preto, SP, CEP: 15.090-000, Brazil.
Mol Biol Rep. 2012 Oct;39(10):9277-84. doi: 10.1007/s11033-012-1629-5. Epub 2012 Aug 19.
Individuals with Down syndrome (DS) carry three copies of the Cystathionine β-synthase (CβS) gene. The increase in the dosage of this gene results in an altered profile of metabolites involved in the folate pathway, including reduced homocysteine (Hcy), methionine, S-adenosylhomocysteine (SAH) and S-adenosylmethionine (SAM). Furthermore, previous studies in individuals with DS have shown that genetic variants in genes involved in the folate pathway influence the concentrations of this metabolism's products. The purpose of this study is to investigate whether polymorphisms in genes involved in folate metabolism affect the plasma concentrations of Hcy and methylmalonic acid (MMA) along with the concentration of serum folate in individuals with DS. Twelve genetic polymorphisms were investigated in 90 individuals with DS (median age 1.29 years, range 0.07-30.35 years; 49 male and 41 female). Genotyping for the polymorphisms was performed either by polymerase chain reaction (PCR) based techniques or by direct sequencing. Plasma concentrations of Hcy and MMA were measured by liquid chromatography-tandem mass spectrometry as previously described, and serum folate was quantified using a competitive immunoassay. Our results indicate that the MTHFR C677T, MTR A2756G, TC2 C776G and BHMT G742A polymorphisms along with MMA concentration are predictors of Hcy concentration. They also show that age and Hcy concentration are predictors of MMA concentration. These findings could help to understand how genetic variation impacts folate metabolism and what metabolic consequences these variants have in individuals with trisomy 21.
患有唐氏综合征（DS）的个体携带三个胱硫醚β-合酶（CβS）基因拷贝。该基因剂量的增加导致叶酸途径中涉及的代谢物谱发生改变，包括降低同型半胱氨酸（Hcy）、蛋氨酸、S-腺苷同型半胱氨酸（SAH）和 S-腺苷甲硫氨酸（SAM）。此外，DS 患者的先前研究表明，参与叶酸途径的基因中的遗传变异会影响该代谢产物的浓度。本研究的目的是研究叶酸代谢相关基因中的多态性是否会影响 DS 个体的 Hcy 和甲基丙二酸（MMA）血浆浓度以及血清叶酸浓度。在 90 名 DS 个体（中位数年龄 1.29 岁，范围 0.07-30.35 岁；49 名男性和 41 名女性）中研究了 12 个与叶酸代谢相关的基因多态性。通过聚合酶链反应（PCR）为基础的技术或直接测序来进行基因分型。如前所述，通过液相色谱-串联质谱法测量 Hcy 和 MMA 的血浆浓度，并使用竞争免疫测定法定量血清叶酸。我们的结果表明，MTHFR C677T、MTR A2756G、TC2 C776G 和 BHMT G742A 多态性以及 MMA 浓度是 Hcy 浓度的预测因子。它们还表明年龄和 Hcy 浓度是 MMA 浓度的预测因子。这些发现可以帮助我们了解遗传变异如何影响叶酸代谢，以及这些变体在 21 三体个体中具有哪些代谢后果。
