The influence of functional polymorphic positions of HLA-DRβ1 molecules on risk for South Indian systemic lupus erythematosus patients.

The aim of this case-control study was to investigate the association of human leukocyte antigen (HLA) Class II alleles with the susceptibility and phenotypic heterogeneity in systemic lupus erythematosus (SLE) in South Indian patients. A total of 439 individuals (212 SLE cases and 227 age- and ethnicity-matched controls) were included in the study. The genotyping of HLA-DRβ1 and - DQβ1 was conducted by the PCR-SSP method. HLA-DRβ107 was significantly associated with SLE (OR: 2.02; 95% CI: 1.34-3.04, p = 1.50 × 10, p = 1.95 × 10), whereas the DRβ114 allele was negatively associated with SLE (OR: 0.49; 95% CI: 0.31-0.76, p = 1.70 × 10, p = 0.221). In addition, the HLA-DRβ107/15 genotype tended to be positively associated with SLE (OR: 3.23, 95% CI: 1.57-6.63, p = 0.0009). Amino acid residues residing in the peptide-binding pocket of HLA-DRβ1 play a significant role in peptide recruitment and antigen presentation. Our results demonstrated that amino acid glycine 11 (OR: 2.11, 95% CI: 1.42-3.12, p = 0.00093), tyrosine 13 (OR: 2.11, 95% CI: 1.42-3.12, p = 0.00062) and glutamine 74 (OR: 2.11, 95% CI: 1.42-3.12, p = 0.00077) showed a significant positive association with SLE. Certain haplotype combinations, DRB107-DQβ103 (OR: 2.21; 95% CI:1.29-3.79, p = 0.06, p =  0.00036) and DRβ107-DQβ105 (OR: 2.51, 95% CI: 1.34-4.71, p = 0.07, p = 0.00039), had positive associations whereas DRβ114-DQβ103 (OR: 0.14, 95% CI: 0.061-0.36, p = 2.34 × 10, p = 1.30 × 10) were found to have a significant negative association with SLE. So far, the present study is the first attempt to investigate the association of HLA-DRβ1 and - DQβ1 allele, genotype and haplotype combinations with the risk of SLE in South Indian patients. In conclusion, the HLA-DRβ107 allele is associated with risk of SLE whereas a protective association of HLA-DRβ1*14 alleles with SLE was observed.