Modification of multiple sclerosis phenotypes by african ancestry at HLA

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

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71 Citations (Scopus)

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 geno-typed 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.

Original languageEnglish
Pages (from-to)226-233
Number of pages8
JournalArchives of Neurology
Volume66
Issue number2
DOIs
Publication statusPublished - 2009 Feb 1

ASJC Scopus subject areas

  • Arts and Humanities (miscellaneous)
  • Clinical Neurology

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    Cree, B. A. C., Reich, D. E., Khan, O., De Jager, P. L., Nakashima, I., Takahashi, T., Bar-Or, A., Tong, C., Hauser, S. L., & Oksenberg, J. R. (2009). Modification of multiple sclerosis phenotypes by african ancestry at HLA. Archives of Neurology, 66(2), 226-233. https://doi.org/10.1001/archneurol.2008.541