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伊朗多发性硬化症患者重金属暴露与 GSTM1 多态性的相关性。

Correlation between heavy metal exposure and GSTM1 polymorphism in Iranian multiple sclerosis patients.

机构信息

Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tehran University of Medical Sciences, Room J-309, P.O. Box: 14155-6451, Tehran, Iran.

Department of Pharmacology and Toxicology, Faculty of Pharmacy, Isfahan University of Medical Sciences, Isfahan, Iran.

出版信息

Neurol Sci. 2017 Jul;38(7):1271-1278. doi: 10.1007/s10072-017-2934-5. Epub 2017 Apr 21.

Abstract

Multiple sclerosis (MS) is an immune-mediated chronic inflammatory disease of the central nervous system. Various exposures to heavy metals can lead to toxicity and oxidative stress. While glutathione-S-transferases are known as oxidative stress-related genes and involved in metal biotransformation. The aim of the present study is to investigate the correlation of GSTM1 polymorphism in MS patients and the possible association with blood concentration of arsenic (As) and cadmium (Cd) as major heavy metal pollutants. This study included 69 relapsing-remitting multiple sclerosis patients and 74 age/gender-matched healthy subjects. The genetic profile was analyzed by PCR, and heavy metal concentrations were measured by electrothermal atomic absorption spectrometry. Our results demonstrated that patients with the GSTM1 null genotype had considerably lower age of onset. However, the frequency of the GSTM1 null genotype was not significantly different between MS and control groups. In addition, the blood As and Cd concentrations were considerably higher in MS patients in comparison with healthy individuals. Also, it revealed that the GSTM1 null genotype associated with high Cd level in MS patients. There was also a trend toward an increase in As level in MS patients. These data may point to susceptibility to cadmium toxicity especially in RR-MS patients with smoking habit. Furthermore, the M1 null genotype will help in a prognosis of MS considering the age of onset. It confirms that the long-term prognosis in MS and patient's disability are influenced by their ability to remove the toxic products and perhaps to decrease oxidative stress.

摘要

多发性硬化症(MS)是一种中枢神经系统的免疫介导的慢性炎症性疾病。各种重金属暴露会导致毒性和氧化应激。虽然谷胱甘肽-S-转移酶被认为是与氧化应激相关的基因,并参与金属的生物转化。本研究旨在探讨 MS 患者 GSTM1 多态性与血液中砷(As)和镉(Cd)浓度的相关性,As 和 Cd 是主要的重金属污染物。本研究纳入了 69 例复发缓解型多发性硬化症患者和 74 名年龄/性别匹配的健康对照者。通过 PCR 分析遗传谱,用电热原子吸收光谱法测量重金属浓度。我们的结果表明,GSTM1 缺失基因型患者的发病年龄明显较低。然而,MS 组和对照组之间 GSTM1 缺失基因型的频率没有显著差异。此外,与健康个体相比,MS 患者的血液 As 和 Cd 浓度明显较高。此外,还发现 GSTM1 缺失基因型与 MS 患者的高 Cd 水平相关。MS 患者的 As 水平也呈上升趋势。这些数据可能表明对镉毒性的易感性,尤其是在有吸烟习惯的 RR-MS 患者中。此外,M1 缺失基因型将有助于考虑发病年龄对 MS 的预后。这证实了 MS 的长期预后和患者的残疾程度受到其清除有毒产物的能力的影响,或许可以减轻氧化应激。

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