Abstract
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 HLA-DRB1*0301 allele in Muslims (PBonferroni=0.004, odds ratio (OR)=3.07), and negative association in Christian Arabs (PBonferroni=0.01, OR=0.12), with similar results obtained for HLA-DQB1*0201. HLA-B*52 was negatively associated with MS only in Muslims (PBonferroni=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.
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Acknowledgements
This study was supported by the National Multiple Sclerosis Society of USA–RG 3520A1/1 (AM); the Wolfson Family Charitable Trust (AM), the Sacta-Rashi Foundation (AM), the Technion's Vice-President for Research funds (AM) and by Grant AI067152 from the National Institutes of Allergy and Infectious Diseases (JRO). We thank the MS patients, their families and the healthy volunteers for participation in this study. We thank Yvonne Nachleh, Anat Volkowich, Matana Galili and Maayan Merhav, Rappaport Faculty of Medicine and Research Institute, Technion–Israel Institute of Technology, Haifa, Israel, for expert technical assistance; Sara Dishon, Carmel Medical Center, Haifa, Israel, for providing patient care and assistance in clinical data management; Dr Ofra Barnett-Griness and Nili Stein Carmel Medical Center, Haifa, Israel, for statistical consultations and Prof Doron Lancet, Weizmann Institute of Science, for critical reviewing of the article.
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Appendix
Appendix
Members of The Israeli MS Genetics Group:
Ester Kahana, MD: Barzilai Medical Center, Ashkelon; Dimitrios Karussis, MD PhD: Hadassah Medical Center, Jerusalem; Rafik Masalha, MD: Soroka Medical Center, Beer-Sheva; Ariel Miller, MD PhD: Carmel Medical Center; Panayiota Petrou, MD: Hadassah Medical Center, Jerusalem; Hana Rawasdeh, MD: Carmel Medical Center, Haifa; Radi Shahein, MD: Sieff Medical Center, Safed.
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Benedek, G., Paperna, T., Avidan, N. et al. Opposing effects of the HLA-DRB1*0301-DQB1*0201 haplotype on the risk for multiple sclerosis in diverse Arab populations in Israel. Genes Immun 11, 423–431 (2010). https://doi.org/10.1038/gene.2010.20
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DOI: https://doi.org/10.1038/gene.2010.20