HLA-DRB1 and multiple sclerosis in Malta

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

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.

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.

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.