The HLA locus and multiple sclerosis in Spain. Role in disease susceptibility, clinical course and response to interferon-beta.

The HLA-DR2 haplotype (DRB1*1501, DQB1*0602) on chromosome 6p21 has consistently demonstrated both association and linkage with multiple sclerosis (MS) in case-control and family studies, particularly in Caucasians of Northern European descent. However, the role of a gene within this region in determining clinical features or response to immunotherapy remains largely unknown. A new familial MS data set from the Mediterranean Spanish Basin was collected according to rigorous ascertainment criteria. We confirm, primarily in the cohort originating from Continental Spain, that similar to other high-risk groups, there was a significant association with HLA-DR2. No other DR or DQ alleles were found to be associated with disease susceptibility nor were alleles at the class I A and B loci. Overall, the effect of HLA appears to be less substantial than that observed in a reference US population with a higher disease incidence. No effect of the HLA-DR2 haplotype on age of onset, initial clinical symptoms and disease course was observed. Similarly, no difference in the distribution of responders and nonresponders to interferon-beta (IFNB) therapy, as defined by primary and secondary end points, was observed when individuals were stratified according to HLA-DR2 status.