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Lipid Peroxidation and Null Glutathione S-Transferase GSTMI Genothpe in Epileptrics with Anticonvulsant Therapy

脂質過氧化產物與缺損型麩胱甘太轉換酵素基因在癲癇患者之研究

摘要


針對54個良好控制癲癇患者及48位頑固型癲癇患者,分別進行缺損劉麩胱甘太轉換酵素基(GSTMI (-))之檢定與脂質過氧化產物(MDA),另同時針對110個健康者做對照組,我們發現頑固型癲癇患者對良好控制癲癇患者俱有高比例之GSTMI(-)(OR=4.7, 95% CI=1.9-11.5, P=0.001),與正常對照組亦有較高比例之GSTMI(-)(OR=2.5, 95% CI=1.0-6.1, P=0.047)。同時這些頑固型癲癇患者對良好控制癲癇患者俱有高比例之MDA(95% CI=0.2-0.9, P=0.002)與正常對照組亦有較高比例之GSTMI(-)(95%世隔絕CI=0.7-2.0, P=0.001)。在頑固型癲癇患者且帶有GSTMI(-)基因,其血清有較高之MDA產生。結論顯示,頑固型癲癇患者常帶有較高比例之GSTMI基因型,其原因可能是此類基因型患者體內無法產生足夠之CST酵素,以致無法完全消除帶有自山基特性之抗癲癇藥物代謝物質,以致造成腦部持續不正常放電。

並列摘要


We examined the null genotype of glutathione S-transferase class μ (GSTMI (-)) and the level of serum lipid peroxides (measured as malondialdehyde, MDA) in 54 epileptics with good seizure control by mono-anticonvulsant therapy and 48 epileptics with intractable seizure under poly-anticonvulsant therapy. One hundred and ten healthy controls were also included. We found that the frequency of GSTMI (-) of the patients of the group with intractable seizure was significantly higher than those of the group with good seizure control (OR=4.7, 95% CI=1.9-11.5, P=0.001) and of the normal healthy subjects (OR=2.5, 95% CI=1.0-6.1, P=0.047). Significant elevation of serum MBA was also noted in the group of patients with intractable seizure as compared with the group of patients with good seizure control (3.4±2.1 μM vs 2.4±0.8 (M, 95% CI=0.2-0.9. P=0.002) and normal subjects (3.4±2.1 μM±1.9±1.1μM 95% CI=0.7-2.0, P=0.001). Moreover, the average serum level of MDA of the patients with GSTMI (-) genotype was higher than that of GSTMI (+) epileptics (3.4±1.8 (μM vs 2.3±0.9 μM, 95% CI=0.3-2.0, P=0.011) with intractable seizure under poly-anticonvulsants therapy. These findings suggest that the GSTMI (-) genotype may be an important genetic factor involved in the response of epileptics patients to conventional anticonvulsant therapy via free radicals-induced lipid peroxidation in the brain.

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