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

L. F. Barcellos, J. R. Oksenberg, A. B. Begovich, E. R. Martin, S. Schmidt, E. Vittinghoff, D. S. Goodin, D. Pelletier, R. R. Lincoln, P. Bucher, A. Swerdlin, M. A. Pericak-Vance, J. L. Haines, S. L. Hauser

Research output: Contribution to journalArticlepeer-review

214 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)710-716
Number of pages7
JournalAmerican journal of human genetics
Issue number3
StatePublished - Mar 1 2003
Externally publishedYes

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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