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HLA-DRB1 and multiple sclerosis in Malta

From the Health Research Board, Dublin, Ireland (G.D.); Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK (T.W.Y., A.G., S.S., D.A.S.C.); Section for Experimental Neurology, Katholieke Universiteit Leuven, Leuven, Belgium (A.G.); Tissue Typing Laboratory, Addenbrooke’s Hospital, Cambridge, UK (C.J.T., R.S.G.); Central Middlesex Hospital, London, UK (M.E.); St. Luke’s Hospital, Guardamangia, MSD09, Malta (A.G.-D., M.V.); Maltese Blood Transfusion Service, Guardamangia, MSD09, Malta (A.A.); and Laboratory of Molecular Genetics, Department of Physiology and Biochemistry, Biomedical Sciences Building, University of Malta, Msida, MSD06, Malta (A.F.).

Address correspondence and reprint requests to Dr. Geoffrey Dean, 39 Nutley Rd., Donnybrook, Dublin 4, Ireland hrb{at}hrb.ie

Background: By comparison with the neighboring island of Sicily, the frequency of multiple sclerosis (MS) in Malta is remarkably low.

Methods: To explore whether the relative rarity of MS in Malta might be the result of lower population frequencies of major histocompatibility complex susceptibility alleles, we genotyped the HLA-DRB1 locus in 77 Maltese-born patients (97% of the prevalent unrelated native cases) and 206 Maltese controls. We made comparisons with previously published data for Sicily and other European countries.

Results: The anticipated association with HLA-DRB1*15, the main susceptibility allele in most other populations, was confirmed (p_c = 0.009) but, in addition, we also observed an equally strong, and apparently protective, effect of the HLA-DRB1*11 allele (p_c = 0.016). In comparison with previously published data from Sicily, we found that all HLA-DRB1 risk alleles were more common in Malta, whereas HLA-DRB1*11 was slightly less common.

Conclusions: The difference in prevalence seen between the neighboring islands of Malta and Sicily cannot be explained by differences in background HLA-DRB1 population allele frequencies, which if anything would predict a higher rate of disease in Malta than in Sicily.

Abbreviations: AFBAC = affected family-based controls; MS = multiple sclerosis; NTrans = nontransmitted; Trans = transmitted.

Editorial, see page 97

e-Pub ahead of print on December 5, 2007, at www.neurology.org.

*These authors contributed equally to this work as first authors.

This project was supported by the Wellcome Trust, the Multiple Sclerosis Societies of Great Britain and Northern Ireland and of the Republic of Ireland, and the NIH. T.W.Y. was supported by the Wellcome Trust and Cambridge Philosophical Society. A.G. is a Postdoctoral Fellow of the Research Foundation–Flanders (FWO–Vlaanderen).

Disclosure: The authors report no conflicts of interest.

Received December 11, 2006. Accepted in final form April 24, 2007.

This article has been cited by other articles:

				S. V. Ramagopalan, D. A. Dyment, A. D. Sadovnick, and G. C. Ebers HLA-DRB1 AND MULTIPLE SCLEROSIS IN MALTA Neurology, October 21, 2008; 71(17): 1379 - 1379. [Full Text] [PDF]

				B. Fontaine and L. F. Barcellos Evidence for a complex interaction between HLA-DRB1 and environmental factors in MS Neurology, January 8, 2008; 70(2): 97 - 98. [Full Text] [PDF]

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