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Arch Neurol. 2009 Feb;66(2):226-33. doi: 10.1001/archneurol.2008.541.

Modification of Multiple Sclerosis Phenotypes by African Ancestry at HLA.

Author information

  • 1Department of Neurology, University of California-San Francisco, USA. bruce.cree@ucsf.edu

Abstract

BACKGROUND:

In those with multiple sclerosis (MS), African American individuals have a more severe disease course, an older age at onset, and more often have clinical manifestations restricted to the optic nerves and spinal cord (opticospinal MS) than white persons.

OBJECTIVE:

To determine whether genetic variation influences clinical MS patterns.

DESIGN:

Retrospective multicenter cohort study.

PARTICIPANTS:

Six hundred seventy-three African American and 717 white patients with MS.

MAIN OUTCOME MEASURES:

Patients with MS were genotyped for HLA-DRB1 and HLA-DQB1 alleles. The proportion of European ancestry at HLA was estimated by genotyping single-nucleotide polymorphisms with known significant frequency differences in West African and European populations. These genotypes were correlated with the opticospinal disease phenotype, disability measures, and age at onset.

RESULTS:

Subjects with DRB1*15 alleles were twice as likely to have typical MS rather than opticospinal MS (P = .001). Of the subjects with opticospinal MS or a history of recurrent transverse myelitis who were seropositive for anti-aquaporin 4 antibodies (approximately 5%), none carried DRB1*15 alleles (P = .008). Independently of DRB1*15, African ancestry at HLA correlated with disability as measured by the Multiple Sclerosis Severity Score (P < .001) and risk of cane dependency (hazard ratio, 1.36; P < .001); DRB1*15 alleles were associated with a 2.1-year earlier age at onset (P < .001).

CONCLUSIONS:

These data indicate that the role of HLA in MS is not limited to disease susceptibility but that genes embedded in this locus also influence clinical outcomes.

PMID:
19204159
[PubMed - indexed for MEDLINE]
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