Association of HLA-DRB1 and-DQB1 alleles and haplotypes with rheumatoid arthritis in a Pakistani population

Introduction: Rheumatoid arthritis is an autoimmune disease with poorly understood pathophysiology. Genetic components of disease etiology, especially human leukocyte antigen (HLA) associations, are well known. Ethnic differences account for a number of variations in disease association with the HLA locus and there seem to be differences in various studies regarding its genetic predisposition. This study was aimed at determining the contribution of DRB1 and DQB1 components of HLA class II in rheumatoid arthritis in a Pakistani cohort. Method: For this study, 110 patients and 120 healthy controls from the same geographical area and matched ethnicity were enrolled. Blood DNA was isolated from all the subjects and HLA alleles were typed following allele specific amplification. Subsequently, haplotypes were generated and allelic and haplotype distribution frequencies were compared among the patients and controls using chi(2) and Arlequin software. The data obtained by this analysis were also compared with other reported associations found in the Pakistani population by meta-analysis. Results: HLA allelic status was determined among the patients and controls from the same geographical area to account for differences in ethnicity and environmental factors. Significant associations were found for alleles as well as haplotypes among the patients of rheumatoid arthritis. DRB1*10, DQB1*05 and DQB1*602 were found to be associated with disease susceptibility, whereas DRB1*11 and DQB1*02 had protective effect against the disease. Similarly, haplotype DRB1*10-DQB1*05 was associated disease risk, whereas DRB1*07-DQB1*02 and DRB1*11-DQB1*0301 had a protective effect. Conclusion: There is a significant DRB1 and DQB1 allele and haplotype association with rheumatoid arthritis susceptibility and protection.