白细胞介素-10启动子多态性与多发性硬化症的严重程度

Promoter polymorphism of IL-10 and severity of multiple sclerosis.

作者信息

Luomala M, Lehtimäki T, Huhtala H, Ukkonen M, Koivula T, Hurme M, Elovaara I

机构信息

Laboratory of Atherosclerosis Genetics, Department of Clinical Chemistry, Centre for Laboratory Medicine, Tampere University Hospital, and University of Tampere, Medical School, Tampere, Finland.

出版信息

Acta Neurol Scand. 2003 Dec;108(6):396-400. doi: 10.1034/j.1600-0404.2003.00165.x.

DOI:10.1034/j.1600-0404.2003.00165.x

PMID:14616291

Abstract

Functional polymorphisms of the genes for interleukin-10 (IL-10; promoter position -1082), chemokine receptor-5 (CCR5 32 bp deletion), tumor necrous factor-alpha (TNFalpha promoter position -308) and cytotoxic T-lymphocyte antigen-4 (CTLA-4 exon 1 position 49) were investigated for possible influence on susceptibility and outcome of multiple sclerosis (MS). The polymorphisms were typed by polymerase chain reaction based methods or by direct sequencing in MS patients (n=93-116) and controls (n=109-400). The studied genes were not associated with MS susceptibility. Patients were classified as suffering from a mild/moderate [Expanded Disability Status Scale (EDSS) 0-5.5] or severe (EDSS 6-8.0) form of MS. The AG genotype of IL-10 proved to be protective against severe MS in all patients (OR=0.32, P=0.010), the effect being increased over the years (10 years; OR=0.33, P=0.043, 15 years; OR=0.21, P=0.025 or 20 years; OR=0.14, P=0.026). Our results suggest that differential production of IL-10 might be a factor in the severity of MS.

摘要

研究了白细胞介素-10（IL-10；启动子位置-1082）、趋化因子受体-5（CCR5 32碱基对缺失）、肿瘤坏死因子-α（TNFα启动子位置-308）和细胞毒性T淋巴细胞抗原-4（CTLA-4外显子1位置49）基因的功能多态性对多发性硬化症（MS）易感性和预后的可能影响。通过基于聚合酶链反应的方法或直接测序对MS患者（n=93-116）和对照（n=109-400）的多态性进行分型。所研究的基因与MS易感性无关。患者被分类为患有轻度/中度[扩展残疾状态量表（EDSS）0-5.5]或重度（EDSS 6-8.0）形式的MS。IL-10的AG基因型被证明对所有患者的重度MS具有保护作用（OR=0.32，P=0.010），随着时间的推移这种作用增强（10年；OR=0.33，P=0.043，15年；OR=0.21，P=0.025或20年；OR=0.14，P=0.026）。我们的结果表明，IL-10的差异产生可能是MS严重程度的一个因素。