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Neurology. 2013 Jul 16;81(3):219-27. doi: 10.1212/WNL.0b013e31829bfe2f. Epub 2013 Jun 14.

Genetic risk variants in African Americans with multiple sclerosis.

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1
Department of Neurology, School of Medicine, University of California, San Francisco, CA, USA.

Abstract

OBJECTIVES:

To assess the association of established multiple sclerosis (MS) risk variants in 3,254 African Americans (1,162 cases and 2,092 controls).

METHODS:

Human leukocyte antigen (HLA)-DRB1, HLA-DQB1, and HLA-A alleles were typed by molecular techniques. Single nucleotide polymorphism (SNP) genotyping was conducted for 76 MS-associated SNPs and 52 ancestry informative marker SNPs selected throughout the genome. Self-declared ancestry was refined by principal component analysis of the ancestry informative marker SNPs. An ancestry-adjusted multivariate model was applied to assess genetic associations.

RESULTS:

The following major histocompatibility complex risk alleles were replicated: HLA-DRB1*15:01 (odds ratio [OR] = 2.02 [95% confidence interval: 1.54-2.63], p = 2.50e-07), HLA-DRB1*03:01 (OR = 1.58 [1.29-1.94], p = 1.11e-05), as well as HLA-DRB1*04:05 (OR = 2.35 [1.26-4.37], p = 0.007) and the African-specific risk allele of HLA-DRB1*15:03 (OR = 1.26 [1.05-1.51], p = 0.012). The protective association of HLA-A*02:01 was confirmed (OR = 0.72 [0.55-0.93], p = 0.013). None of the HLA-DQB1 alleles were associated with MS. Using a significance threshold of p < 0.01, outside the major histocompatibility complex region, 8 MS SNPs were also found to be associated with MS in African Americans.

CONCLUSION:

MS genetic risk in African Americans only partially overlaps with that of Europeans and could explain the difference of MS prevalence between populations.

PMID:
23771490
PMCID:
PMC3770164
DOI:
10.1212/WNL.0b013e31829bfe2f
[Indexed for MEDLINE]
Free PMC Article
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