HLA-DRB1 and multiple sclerosis in Malta

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.