HLA-DR2 dose effect on susceptibility to multiple sclerosis and influence on disease course

被引：203
作者：
Barcellos, LF
Oksenberg, JR
Begovich, AB
Martin, ER
Schmidt, S
Vittinghoff, E
Goodin, DS
Pelletier, D
Lincoln, RR
Bucher, P
Swerdlin, A
Perick-Vance, MA
Haines, JL
Hauser, SL
机构：
[1] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA
[2] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA
[3] Roche Mol Syst, Dept Human Genet, Alameda, CA USA
[4] Duke Univ, Med Ctr, Dept Med, Ctr Human Genet, Durham, NC 27710 USA
[5] Vanderbilt Univ, Dept Mol Physiol & Biophys, Program Human Genet, Nashville, TN 37232 USA
来源：
AMERICAN JOURNAL OF HUMAN GENETICS | 2003年 / 72卷 / 03期
关键词：
D O I：
10.1086/367781
中图分类号：
Q3 [遗传学];
学科分类号：
071007 ; 090102 ;
摘要：
Models of disease susceptibility in multiple sclerosis (MS) often assume a dominant action for the HLA-DRB1* 1501 allele and its associated haplotype (DRB1* 1501-DQB1* 0602 or DR2). A robust and phenotypically well-characterized MS data set was used to explore this model in more detail. A dose effect of HLA-DR2 haplotypes on MS susceptibility was revealed. This observation suggests that, in addition to the role of HLA-DR2 in MS, two copies of a susceptibility haplotype further increase disease risk. Second, we report that DR2 haplotypes modify disease expression. There is a paucity of benign MS and an increase of severe MS in individuals homozygous for DR2. Concepts of the molecular mechanisms that underlie linkage and association of the human leukocyte antigen (HLA) region to MS need to be revised to accommodate these data.
引用
收藏
页码：710 / 716
页数：7
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