POLYMORPHISM OF HLA-DRB, HLA-DQA1, AND HLA-DQA1 IN RHEUMATOID-ARTHRITIS IN ASIAN INDIANS - ASSOCIATION WITH DRB1-ASTERISK-0405 AND DRB1-ASTERISK-1001

We investigated the DRB, DQA1, and DQB1 polymorphism and haplotypes in sporadic and familial RA subjects of Asian Indian origin by PCR oligo typing using biotinylated SSOPs. Molecular subtyping of DRB104 in RA patients showed strongest association with highest relative risk with DRB10405, followed by DRB1*0401. A significant decreased frequency of DRB11502 was observed in patients compared to controls (chi(2) = 4.5 ). Among other alleles, DRB1001 was found to be significantly increas ed. A total of 73.3% of patients carried the shared sequence of the th ird HVR (67-74) of DRB1 domain compared to its presence in only 37.6% of controls. A significant number of patients carried DR4 haplotypes o n DQB10302 (58%) as against loci. DQB1*0301 which was present only on 10.5% of the haplotypes. When compared to controls, the difference wa s significant for the latter allele only. Few unique DR-DQ haplotypes were observed in Asian Indians. Among DR-DQ haplotypes, DRB10401-DQB1 0302 gave the highest risk whereas DRB1*0403-DQB1*0301 was negatively associated. Alleles with negative charge at position 70 confer protec tion or are negatively associated with RA whereas among the associated alleles, glycine at position 86 resulted in higher risk than those wi th valine at this position. A heterogenous association of DQB1 alleles with DR4 subtypes, influencing susceptibility to RA, suggests the DQB locus is not primarily associated with RA and susceptibility lies in the sequence 67-74 of the DRB1 loci.