HLA-DQ association and allele competition in Chinese narcolepsy.

Tissue antigens Pub Date : 2012-10-01 Epub Date: 2012-08-04 DOI:10.1111/j.1399-0039.2012.01948.x
F Han, L Lin, J Li, S X Dong, P An, L Zhao, N Y Liu, Q Y Li, H Yan, Z C Gao, J Faraco, K P Strohl, X Liu, H Miyadera, E Mignot
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引用次数: 53

Abstract

In Japanese, Koreans and Caucasians, narcolepsy/hypocretin deficiency is tightly associated with the DRB1*15:01-DQA1*01:02-DQB1*06:02 haplotype. Studies in African-Americans suggest a primary effect of DQB1*06:02, but this observation has been difficult to confirm in other populations because of high linkage disequilibrium between DRB1*15:01/3 and DQB1*06:02 in most populations. In this study, we studied human leucocyte antigen (HLA) class II in 202 Chinese narcolepsy patients (11% from South China) and found all patients to be DQB1*06:02 positive. Comparing cases with 103 unselected controls, and 110 and 79 controls selected for the presence of DQB1*06:02 and DRB1*15:01, we found that the presence of DQB1*06:02 and not DRB1*15:01 was associated with narcolepsy. In particular, Southern Chinese haplotypes such as the DRB1*15:01-DQA1*01:02-DQB1*06:01 and DRB1*15:01-DQA1*01:02-DQB1*05 were not associated with narcolepsy. As reported in Japanese, Koreans, African-Americans and Caucasians, additional protective effects of DQA1*01 (non-DQA1*01:02) and susceptibility effects of DQB1*03:01 were observed. These results illustrate the extraordinary conservation of HLA class II effects in narcolepsy across populations and show that DRB1*15:01 has no effect on narcolepsy susceptibility in the absence of DQB1*06:02. The results are also in line with a previously proposed 'HLA-DQ allelic competition model' that involves competition between non-DQA1*01:02, non-DQB1*06:02 'competent' (able to dimerize together) DQ1 alleles and the major DQα*01:02/ DQβ*06:02 narcolepsy heterodimer to reduce susceptibility.

中国嗜睡症患者HLA-DQ相关性及等位基因竞争。
在日本人、韩国人和高加索人中,发作性睡病/下丘脑分泌素缺乏与DRB1*15:01-DQA1*01:02-DQB1*06:02单倍型密切相关。对非裔美国人的研究表明DQB1*06:02的主要影响,但由于在大多数人群中DRB1*15:01/3和DQB1*06:02之间的连锁高度不平衡,这一观察结果很难在其他人群中得到证实。本研究对202例中国发作性睡病患者(11%来自华南地区)进行了人白细胞抗原(HLA)ⅱ类检测,发现所有患者均为DQB1*06:02阳性。将103例未选择的对照,以及110例和79例选择存在DQB1*06:02和DRB1*15:01的对照进行比较,我们发现存在DQB1*06:02而不存在DRB1*15:01与嗜睡症有关。特别是,DRB1*15:01-DQA1*01:02-DQB1*06:01和DRB1*15:01-DQA1*01:02-DQB1*05等单倍型与嗜睡症无关。据报道,在日本、韩国、非洲裔美国人和高加索人中,DQA1*01(非DQA1*01:02)具有额外的保护作用,DQB1*03:01具有易感作用。这些结果说明了HLA II类在不同人群中对发作性睡病的特殊保护作用,并表明在缺乏DQB1*06:02的情况下,DRB1*15:01对发作性睡病的易感性没有影响。该结果也符合先前提出的“HLA-DQ等位基因竞争模型”,该模型涉及非dqa1 *01:02,非dqb1 *06:02“有能力”(能够一起二聚)的DQ1等位基因与主要的DQα*01:02/ DQβ*06:02异源二聚体之间的竞争,以降低嗜睡症的易感性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Tissue antigens
Tissue antigens 医学-病理学
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