Glutathione S-transferase polymorphisms in MS - Their relationship to disability
Glutathione S-transferase polymorphisms in MS - Their relationship to disability
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DOI：
10.1212/wnl.54.3.552
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发表时间：
2000-02-08
期刊：
影响因子：
9.9
通讯作者：
Hawkins, CP
中科院分区：
文献类型：
--
作者：
Mann, CLA;Davies, MB;Hawkins, CP
背景：氧化应激与炎性脱髓鞘有关。谷胱甘肽S转移酶(GST)超基因家族编码的同工酶似乎在抵抗氧化应激中起关键作用。某些GST基因座是多态的，表明等位基因为空(GSTM1/GSTT1)、编码低活性变异体(GSTP1)或与可变诱导性相关(GSTM3)。目的：探讨GSTM1、GSTM3、GSTT1、GSTP1等位基因变异与多发性硬化临床结局的关系。残疾评定采用Kurtzke扩展残疾状况量表(EDSS)。残疾分为轻度(EDSS 0~4)、中度(4.5~5.5)、重度(EDSS 6~10)。用从淋巴细胞中提取的DNA进行基于聚合酶链式反应的基因分型。通过Logistic回归分析，性别、发病年龄和病程对GST基因分型和临床结果的显著相关性进行了校正。结果：GSTM3AA型与病程10年以上的重度残疾相关(P=0.027，n=177，OR=2.4，95%CI=1.1~5.0)。GSTM1*0.022和GSTP1Ile(105)纯合子与病程超过10年的患者的严重残疾相关(P=0.022，n=179，OR=5.0，95%CI=1.3~19.8)。结论：我们的结果提示MS的长期预后受基因决定的清除氧化应激有毒产物的能力的影响。
Background: Oxidative stress has been implicated in inflammatory demyelination. The glutathione S-transferase (GST) supergene family encodes isoenzymes that appear to be critical in protection against oxidative stress. Certain GST loci are polymorphic, demonstrating alleles that are null (GSTM1/GSTT1), encode low activity variants (GSTP1), or are associated with variable inducibility (GSTM3). Objectives: To investigate the association between clinical outcome in MS and allelic variants of GSTM1, GSTM3, GSTT1, and GSTP1, Methods: Four hundred patients with clinically definite MS were studied. Disability was measured using the Kurtzke Expanded Disability Status Scale (EDSS). Disability was graded as mild (EDSS 0-4), moderate (4.5-5.5), or severe (EDSS 6-10). PCR-based genotyping was performed using DNA extracted from lymphocytes. Significant associations between GST genotypes and clinical outcome were corrected for gender, onset age, and disease duration using logistic regression. Results: We found that the GSTM3 AA genotype was associated with severe disability in patients with a disease duration of more than 10 years (p = 0.027, n = 177, OR = 2.4, 95% CI = 1.1-5.0). Homozygosity for both GSTM1*0 and GSTP1*Ile(105) containing allele was associated with severe disability in patients with a disease duration greater than 10 years (p = 0.022, n = 179, OR = 5.0, 95% CI = 1.3-19.8), Conclusions: Our results suggest that long-term prognosis in MS is influenced by a genetically determined ability to remove the toxic products of oxidative stress.