ASSOCIATION OF HLA-DR4-DW15 (DRB1-ASTERISK-0405) AND DR10 WITH RHEUMATOID-ARTHRITIS IN A SPANISH POPULATION

Objective. To analyze the associations of HLA class II antigens with r heumatoid arthritis (RA) in a Spanish population. Methods. We used DNA oligotyping to determine DR types, DQA1 and DQB1 alleles, and DR4 var iants in 70 unrelated seropositive RA patients and 189 healthy control s living in Spain. Results. A significantly higher frequency of DR4 wa s seen in RA patients compared with controls (relative risk [RR] = 2,4 0). The DR10 specificity correlated most strongly with disease suscept ibility (RR = 3.84). A significant decrease in the frequency of DR7 wa s observed in the RA patients (RR = 0.48). DR4-Dw15 (DRB10405) was fo und to be the unique DR4 allele associated with RA (RR = 4.27, P < 0.0 5), whereas Dw4 (DRB10401) and Dw14 (DRB1*0404/0408) showed no associ ation, and both Dw10 (RRB10402) and Dw13 (DRB1*0403/0407) were negati ve risk factors for the disease. Approximately one-third of the cases of RA could not be explained by the ''shared epitope'' hypothesis. Inv estigation of the DQ alleles associated with DR4 showed that the haplo type Dw15-DQ8 (DRB10405-DQB1*0302) was a susceptibility factor for RA (RR = 6.36, P < 0.05). Conclusion. Our results suggest that HLA class II alleles involved in RA susceptibility can vary among different Cau casian populations.