Katkam S K, Rajasekhar L, Kutala V K
1 Department of Clinical Pharmacology and Therapeutics, 28605 Nizam's Institute of Medical Sciences (NIMS) , Telangana, Hyderabad, India.
2 Department of Clinical Immunology and Rheumatology, 28605 Nizam's Institute of Medical Sciences (NIMS) , Telangana, Hyderabad, India.
Lupus. 2018 May;27(6):991-1000. doi: 10.1177/0961203318759200. Epub 2018 Feb 13.
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.
本病例对照研究的目的是调查人类白细胞抗原（HLA）II类等位基因与南印度系统性红斑狼疮（SLE）患者易感性及表型异质性之间的关联。该研究共纳入439名个体（212例SLE患者和227名年龄及种族匹配的对照）。采用聚合酶链反应-序列特异性引物（PCR-SSP）方法对HLA-DRβ1和-DQβ1进行基因分型。HLA-DRβ107与SLE显著相关（比值比：2.02；95%可信区间：1.34 - 3.04，p = 1.50×10，p = 1.95×10），而DRβ114等位基因与SLE呈负相关（比值比：0.49；95%可信区间：0.31 - 0.76，p = 1.70×10，p = 0.221）。此外，HLA-DRβ107/15基因型与SLE呈正相关趋势（比值比：3.23，95%可信区间：1.57 - 6.63，p = 0.0009）。位于HLA-DRβ1肽结合口袋中的氨基酸残基在肽募集和抗原呈递中起重要作用。我们的结果表明，氨基酸甘氨酸11（比值比：2.11，95%可信区间：1.42 - 3.12，p = 0.00093）、酪氨酸13（比值比：2.11，95%可信区间：1.42 - 3.12，p = 0.00062）和谷氨酰胺74（比值比：2.11，95%可信区间：1.42 - 3.12，p = 0.00077）与SLE呈显著正相关。某些单倍型组合，DRB107-DQβ103（比值比：2.21；95%可信区间：1.29 - 3.79，p = 0.06，p = 0.00036）和DRβ107-DQβ105（比值比：2.51，95%可信区间：1.34 - 4.71，p = 0.07，p = 0.00039）呈正相关，而DRβ114-DQβ103（比值比：0.14，95%可信区间：0.061 - 0.36，p = 2.34×10，p = 1.30×10）与SLE呈显著负相关。迄今为止，本研究是首次尝试调查HLA-DRβ1和-DQβ1等位基因、基因型及单倍型组合与南印度患者SLE风险之间的关联。总之，HLA-DRβ107等位基因与SLE风险相关，而观察到HLA-DRβ1*14等位基因对SLE具有保护作用。
