Mapping multiple sclerosis susceptibility to the HLA-DR locus in African Americans
Mapping multiple sclerosis susceptibility to the HLA-DR locus in African Americans
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DOI：
10.1086/380997
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发表时间：
2004-01-01
影响因子：
9.8
通讯作者：
Hauser, SL
中科院分区：
文献类型：
--
作者：
Oksenberg, JR;Barcellos, LF;Hauser, SL
多发性硬化症 (MS) 存在潜在的复杂遗传易感性，并且与 HLA-DRB1* 1501-DQB1* 0602 单倍型的关联已在高危（北欧）人群中得到反复证明。目前尚不清楚该效应是否由易感性单倍型内的 HLA-DRB1 或 HLA-DQB1 基因解释，它们处于强连锁不平衡 (LD) 状态。与北欧人相比，非洲人群的特点是具有更大的单倍型多样性和独特的 LD 模式。为了更好地定位与 MS 易感性有关的 HLA 基因，在大型且特征明确的非裔美国人数据集中对 DRB1 和 DQB1 基因座进行了病例对照和基于家族的关联研究。揭示了与 HLA-DRB1* 15 的选择性关联，表明 DRB1 位点在 MS 中的主要作用独立于 DQB1*0602。这一发现不太可能仅仅用混合来解释，因为非裔美国多发性硬化症患者的易感性染色体中很大一部分表现出与非洲起源一致的单倍型。
An underlying complex genetic susceptibility exists in multiple sclerosis ( MS), and an association with the HLA-DRB1* 1501-DQB1* 0602 haplotype has been repeatedly demonstrated in high-risk ( northern European) populations. It is unknown whether the effect is explained by the HLA-DRB1 or the HLA-DQB1 gene within the susceptibility haplotype, which are in strong linkage disequilibrium (LD). African populations are characterized by greater haplotypic diversity and distinct patterns of LD compared with northern Europeans. To better localize the HLA gene responsible for MS susceptibility, case-control and family-based association studies were performed for DRB1 and DQB1 loci in a large and well-characterized African American data set. A selective association with HLA-DRB1* 15 was revealed, indicating a primary role for the DRB1 locus in MS independent of DQB1*0602. This finding is unlikely to be solely explained by admixture, since a substantial proportion of the susceptibility chromosomes from African American patients with MS displayed haplotypes consistent with an African origin.