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3235682 
Journal Article 
HLA-DR2 dose effect on susceptibility to multiple sclerosis and influence on disease course 
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; Multiple Sclerosis Genetics Grp 
2003 
Yes 
American Journal of Human Genetics
ISSN: 0002-9297
EISSN: 1537-6605 
72 
3 
710-716 
WOS:000181152600020 
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.