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拉丁美洲多发性硬化症患者 HLA Ⅱ类基因多态性研究。

HLA class II polymorphism in Latin American patients with multiple sclerosis.

机构信息

Center for Autoimmune Diseases Research (CREA), School of Medicine and Health Sciences, Universidad del Rosario, Bogotá, Colombia.

出版信息

Autoimmun Rev. 2010 Apr;9(6):407-13. doi: 10.1016/j.autrev.2009.11.001. Epub 2009 Nov 5.

Abstract

OBJECTIVE

To identify HLA-DRB1 alleles contributing to susceptibility to multiple sclerosis (MS) in a Colombian population and to estimate the common effect size of HLA class II on MS susceptibility in Latin American populations through a meta-analysis.

METHODS

A total of 65 Colombian patients with MS and 184 matched controls were included. HLA-DRB1 typing was done using the sequence-specific oligonucleotide probe method. A bivariate and a multivariate logistic regression analyses were done. Case-control studies performed in Latin America were searched up to January 2009 through a systematic review of the literature. Effect summary odds ratios (ORs) and 95% confidence intervals (CIs) were obtained by means of the random effect model.

RESULTS

A total of 464 cases and 2581 controls from 7 studies and the results of the present study in Colombians were analyzed. HLA-DRB115 (OR: 2.3; 95% CI: 1.68-3.07; p<0.001) and HLA-DQB106 (OR: 2.2; 95% CI: 1.54-3.07; p<0.001) groups as well as DRB11501 (OR: 2.6; 95% CI: 1.67-4.02; p<0.001), DRB11503 (OR: 2.2; 95% CI: 1.39-3.62; p=0.001) and DQB10602 (OR: 2.5; 95% CI: 1.66-3.71; p<0.001) alleles were found to be risk factors for MS. The myelin basic protein immunodominant sequence (221)VHFFKNIVT(229) was predicted to strongly and simultaneously bind to HLA-DRB11501 and *1503.

CONCLUSION

The current study highlights the effect size of HLA class II in MS in Latin America and confirms similar allelic risk factors across diverse populations. Receptor-ligand interactions in the HLA-antigenic peptide complex could have potential predictive and therapeutical implications.

摘要

目的

在哥伦比亚人群中鉴定与多发性硬化症(MS)易感性相关的 HLA-DRB1 等位基因,并通过荟萃分析估计 HLA Ⅱ类在拉丁美洲人群中对 MS 易感性的常见效应大小。

方法

共纳入 65 例哥伦比亚 MS 患者和 184 例匹配对照。采用序列特异性寡核苷酸探针方法进行 HLA-DRB1 分型。进行了双变量和多变量逻辑回归分析。通过系统文献回顾,检索至 2009 年 1 月拉丁美洲进行的病例对照研究。采用随机效应模型获得效应总结比值比(OR)和 95%置信区间(CI)。

结果

分析了来自 7 项研究的共 464 例病例和 2581 例对照,以及哥伦比亚的本研究结果。HLA-DRB115(OR:2.3;95%CI:1.68-3.07;p<0.001)和 HLA-DQB106(OR:2.2;95%CI:1.54-3.07;p<0.001)组以及 DRB11501(OR:2.6;95%CI:1.67-4.02;p<0.001)、DRB11503(OR:2.2;95%CI:1.39-3.62;p=0.001)和 DQB10602(OR:2.5;95%CI:1.66-3.71;p<0.001)等位基因被发现是 MS 的危险因素。髓鞘碱性蛋白免疫显性序列(221)VHFFKNIVT(229)被预测为同时强烈结合 HLA-DRB11501 和 *1503。

结论

本研究强调了 HLA Ⅱ类在拉丁美洲 MS 中的效应大小,并证实了不同人群中存在相似的等位基因危险因素。HLA-抗原肽复合物中的受体-配体相互作用可能具有潜在的预测和治疗意义。

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