IMPORTANCE OF HLA-DRB1 AND DQA1 GENES AND OF THE AMINO-ACID POLYMORPHISMS IN THE FUNCTIONAL DOMAIN OF DR-BETA-1 CHAIN IN MULTIPLE-SCLEROSIS

The association of some HLA class IT alleles with multiple sclerosis (MS) has been amply documented. In the present study the role of HLA class II haplotypes and genotypes and of polymorphic amino acids at the DR alpha 1 locus, located in the antigen binding groove and the CD4 binding domain of the DR alpha 1 chain, were studied in 78 unrelated Caucasian chronic progressive MS (CP MS) patients and 204 controls. The results confirmed the positive association of the DRB1*1501 allele and through linkage also of the DRB1*1501-DQA1*0102 haplotype with MS. In addition, the results showed that the DRB1*1501/DRB1*0400 or DR beta 1(Ala71+His13+) genotype conferred the highest relative risk for MS (RR = 9.14). Alleles encoding for DR beta 1(Phe47+), DR beta 1(Asp70+) and DR beta 1(Thr140+), DQ alpha 1(Phe25+), DQ alpha 1(Leu69+) residues were protective and the highest protection (RR = 0.24) was provided by the DR beta 1(Phe47+)- DQ alpha 1(Phe25+) and DR beta 1(Ser13+)-DQ alpha 1(Phe25+) haplotypes. Our results suggest that both DQ and DR alpha beta heterodimers might contribute to the increased or decreased risk to develop MS by the shape of their antigen-binding groove.