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

Modification of Multiple Sclerosis Phenotypes by African Ancestry at HLA

Bruce A C Cree  1 , David E Reich, Omar Khan, Philip L De Jager, Ichiro Nakashima, Toshiyuki Takahashi, Amit Bar-Or, Christine Tong, Stephen L Hauser, Jorge R Oksenberg
Affiliations
Multicenter Study

Modification of Multiple Sclerosis Phenotypes by African Ancestry at HLA

Bruce A C Cree et al. Arch Neurol. 2009 Feb.

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.

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Figures

Figure
Figure
The DRB1*15 allele frequency in patients with classic multiple sclerosis (MS) or opticospinal MS and healthy controls. In African Americans, DRB1*15 alleles are more often associated with a classic/multifocal rather than an opticospinal disease type.
See this image and copyright information in PMC

References

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