HLA-DR2 dose effect on susceptibility to multiple sclerosis and influence on disease course.
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.
Duke Scholars
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Related Subject Headings
- Risk Assessment
- Phenotype
- Multiple Sclerosis
- Male
- Humans
- Haplotypes
- HLA-DRB1 Chains
- HLA-DR2 Antigen
- HLA-DR Antigens
- Genotype
Citation
Published In
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Risk Assessment
- Phenotype
- Multiple Sclerosis
- Male
- Humans
- Haplotypes
- HLA-DRB1 Chains
- HLA-DR2 Antigen
- HLA-DR Antigens
- Genotype