Interaction of loci within the HLA region influences multiple sclerosis course in the Sardinian population

We examined the influence of alleles at the HLA loci, previously found to be associated with multiple sclerosis (MS) in Sardinia, on the clinical course of the disease in 835 relapsing (R) and 100 primary progressive (PP) patients. Multivariate analysis was carried out on predisposing 0301 or non–associated DPB1 alleles, susceptible or non–associated DRB1–DQB1 haplotypes, both predisposing and non–predisposing, and negatively and non–negatively associated D6S1683 alleles, taking interaction between them into account. Intra–patient analysis showed that the presence of the susceptible or protective D6S1683 allele interacting with predisposing DP 0301 modulated risk of PP disease. These findings suggest that a locus telomeric to HLA class I exerts an effect on alleles at the DPB1 locus in modulating disease course.