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  • Title: The influence of functional polymorphic positions of HLA-DRβ1 molecules on risk for South Indian systemic lupus erythematosus patients.
    Author: Katkam SK, Rajasekhar L, Kutala VK.
    Journal: Lupus; 2018 May; 27(6):991-1000. PubMed ID: 29439646.
    Abstract:
    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-DRβ1*07 was significantly associated with SLE (OR: 2.02; 95% CI: 1.34-3.04, p = 1.50 × 10-4, pc = 1.95 × 10-3), whereas the DRβ1*14 allele was negatively associated with SLE (OR: 0.49; 95% CI: 0.31-0.76, p = 1.70 × 10-2, pc = 0.221). In addition, the HLA-DRβ1*07/15 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, pc = 0.00093), tyrosine 13 (OR: 2.11, 95% CI: 1.42-3.12, pc = 0.00062) and glutamine 74 (OR: 2.11, 95% CI: 1.42-3.12, pc = 0.00077) showed a significant positive association with SLE. Certain haplotype combinations, DRB1*07-DQβ1*03 (OR: 2.21; 95% CI:1.29-3.79, pc = 0.06, p =  0.00036) and DRβ1*07-DQβ1*05 (OR: 2.51, 95% CI: 1.34-4.71, pc = 0.07, p = 0.00039), had positive associations whereas DRβ1*14-DQβ1*03 (OR: 0.14, 95% CI: 0.061-0.36, pc = 2.34 × 10-5, p = 1.30 × 10-6) 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-DRβ1*07 allele is associated with risk of SLE whereas a protective association of HLA-DRβ1*14 alleles with SLE was observed.
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