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Modification of Multiple Sclerosis Phenotypes by African Ancestry at HLA

2009; American Medical Association; Volume: 66; Issue: 2 Linguagem: Inglês

10.1001/archneurol.2008.541

1538-3687

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

Immunotherapy and Immune Responses

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 (PϽ.001) and risk of cane dependency (hazard ratio, 1.36; P Ͻ.001); DRB1*15 alleles were associated with a 2.1year earlier age at onset (P Ͻ .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.