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 cl ass II haplotypes and genotypes and of polymorphic amino acids at the DR alpha 1 locus, located in the antigen binding groove and the CD4 bi nding domain of the DR alpha 1 chain, were studied in 78 unrelated Cau casian chronic progressive MS (CP MS) patients and 204 controls. The r esults confirmed the positive association of the DRB11501 allele and through linkage also of the DRB11501-DQA1*0102 haplotype with MS. In addition, the results showed that the DRB11501/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+) an d 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 al pha 1(Phe25+) haplotypes. Our results suggest that both DQ and DR alph a beta heterodimers might contribute to the increased or decreased ris k to develop MS by the shape of their antigen-binding groove.