口服还原型谷胱甘肽治疗不同基因型高同型半胱氨酸血症的临床观察

Clinical Efficacy of Oral Reduced Glutathione in Hyperhomocysteinemia Patients with Different Genotype

关键词:  还原型谷胱甘肽  叶酸  同型半胱氨酸  亚甲基四氢叶酸还原酶  基因多态性

Key words:  reduced glutathione  folic acid  homocysteine  methylenetetrahydrofolate reductase  gene polymorphism

摘要:

目的 观察口服还原型谷胱甘肽（glutathione，GSH）对亚甲基四氢叶酸还原酶（methylenetetrahydrofolate reductase，MTHFR）不同基因型高同型半胱氨酸血症（hyperhomocysteinemia，HHcy）的治疗效果。方法 107例HHcy患者被分为G组（55例，口服GSH 0.2 g bid）和F组（52例，口服叶酸片0.4 mg bid）。所有患者抽取外周血提取DNA，通过聚合酶链反应-芯片杂交法进行MTHFR C677T位点的基因分型（CC型、CT型和TT型）。12个月后比较2组的总体平均血清同型半胱氨酸（homocysteine，Hcy）浓度，以及2组中MTHFR C677T位点不同基因型患者的平均Hcy浓度。结果 12个月后，G组、F组Hcy浓度均显著低于治疗前（P<0.01），G组与F组比较差异无统计学意义；在不同基因型患者，G组、F组Hcy浓度均低于治疗前；但在CC型患者，G组Hcy浓度降低较F组更明显（10.3±3.2 μmol·L^-1 vs 15.5±3.6 μmol·L^-1，P<0.01）；在CT型患者，2组治疗后Hcy浓度差异无统计学意义；而在TT型患者，F组Hcy浓度降低较G组更明显（26.7±9.8 μmol·L^-1 vs 45.5±10.6μmol·L^-1，P<0.01）。结论 GSH能有效降低Hcy，总体降低Hcy浓度效应与叶酸相近。但在MTHFR C677T CC型及TT型HHcy患者中，GSH与叶酸降低Hcy的作用有差异。GSH可作为治疗HHcy药物之一，尤其对MTHFR C677T CC型HHcy患者，建议优先推荐应用。

Abstract:

OBJECTIVE To study the effects of reduced glutathione(GSH) by oral in hyperhomocysteinemia(HHcy) patients with different methylenetetrahydrofolate reductase(MTHFR) C667T point genotype. METHODS One hundred and seven patients with HHcy were randomized divided into 2 groups:group G(n=55, GSH 0.2 g bid), group F(n=52, folic acid tablets 0.4 mg bid). In all patients, the genomic DNA was extracted from the peripheral blood by using Genomic DNA kit, and single nucleotide polymorphisms of MTHFR C667T was genotyped by PCR-chip hybridization(type CC, CT and TT). The total average serum homocysteine(Hcy) as well as the average serum Hcy of each genotype patients between the 2 groups were compared after 12 months. RESULTS After 12 months, compared with before treatment, the average serum Hcy of group G and group F decreased significantly(P<0.01), but there was not significant difference between the 2 groups. The average serum Hcy of each genotype patients in group G and group F decreased significantly. But for type CC patients, the average serum Hcy of group G decreased lower than group F(10.3±3.2 μmol·L^-1 vs 15.5±3.6 μmol·L^-1, P<0.01). For type CT patients, there was not significant difference between group G and group F. While for type TT patients, the average serum Hcy of group F decreased lower than group G(26.7±9.8 μmol·L^-1 vs 45.5±10.6 μmol·L^-1, P<0.01). CONCLUSION GSH can effectively reduce Hcy, and the overall effect of reducing Hcy concentration is similar to that of folic acid. But in MTHFR C677T CC and TT HHcy patients, the effects between GSH and folic acid may be different. GSH may be an effective method to treat HHcy, especially to those patients with HHcy of CC genotype of MTHFR C677T.