Journal
GENES AND IMMUNITY
Volume 11, Issue 5, Pages 423-431Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/gene.2010.20
Keywords
association studies; autoimmune disease; human leukocyte antigen; major histocompatibility complex; multiple sclerosis; population genetics
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Funding
- National Multiple Sclerosis Society [USA-RG 3520A1/1]
- Wolfson Family Charitable Trust
- Sacta-Rashi Foundation
- Technion's Vice-President for Research
- National Institutes of Allergy and Infectious Diseases [AI067152]
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Different multiple sclerosis (MS) prevalence rates were reported for Muslim and Christian Arabs in Israel. In this study, we evaluated whether associations of human leukocyte antigen (HLA) genes with MS may contribute to this prevalence difference. DNA samples from Israeli Arab MS patients (n 109) and controls (n 132) were typed for HLA class I (HLA-A, -B and -C) and II (HLA-DRB1 and -DQB1) genes. Global comparisons of HLA allele frequencies revealed significant differences between Christians and Muslims; therefore, case-control analyses were stratified by religious affiliation. Disease characteristics of Muslim and Christian Arab MS patients were similar to those reported for European populations. Opposing association signals with MS were observed for alleles composing the DRB1*0301-DQB1*0201 haplotype: positive association of the HLADRB1*0301 allele in Muslims (P Bonferroni 0.004, odds ratio (OR) 3.07), and negative association in Christian Arabs (P(Bonferroni) = 0.01, OR = 0.12), with similar results obtained for HLA-DQB1* 0201. HLA-B*52 was negatively associated with MS only in Muslims (P(Bonferroni) = 0.01, OR = 0.03). The study presents for the first time a high-resolution HLA gene analysis in clinically well-characterized Arab populations with MS, and shows the population-specific contribution of the DRB1*0301-DQB1*0201 haplotype to disease susceptibility. Genes and Immunity (2010) 11, 423-431; doi: 10.1038/gene.2010.20; published online 13 May 2010
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