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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Barcellos, LF; Oksenberg, JR; Begovich, AB; Martin, ER; Schmidt, S; Vittinghoff, E; Goodin, DS; Pelletier, D; Lincoln, RR; Bucher, P; Swerdlin, A; Pericak-Vance, MA; Haines, JL; Hauser, SL; Multiple Sclerosis Genetics Group,

Published Date

  • March 2003

Published In

Volume / Issue

  • 72 / 3

Start / End Page

  • 710 - 716

PubMed ID

  • 12557126

Pubmed Central ID

  • 12557126

International Standard Serial Number (ISSN)

  • 0002-9297

Digital Object Identifier (DOI)

  • 10.1086/367781

Language

  • eng

Conference Location

  • United States