Associations of HLA-DRB1, DQB1 and DPB1 alleles with pulmonary tuberculosis in South India

Abstract

Setting: Tuberculosis is endemic in south India: sputum positive pulmonary tuberculosis is predisposed by HLA-DR2 in south India and few other populations of the world. Objective: To study HLA-DRB1, DQB1, DQA1 and DPB1 allelic polymorphism in pulmonary tuberculosis patients and endemic controls from south India. Design: One hundred and twenty-six, sputum positive pulmonary tuberculosis patients and 87, endemic controls, from Madurai were studied for MHC class II allelic polymorphism by PCR-SSOP method. XI IHWC primers and probes and non-radioactive probing methods were employed. Results: HLA DRB1^∗1501 and DQB1^∗0601 predisposed for pulmonary tuberculosis (DRB1^∗1501: odds ratio (OR)=2.68, 95% confidence interval (CI)=1.30–5.89, P value (P)=0.013, aetiological fraction (EF)=0.17; DQB1^∗0601: OR=2.32, CI=1.29–4.27, P=0.008, EF=0.26). Haplotype DRB1^∗1501–DQB1^∗0601 was higher in patients (1324 per 10000, X²=27.07) than controls (F=404÷10000, X²=8.84). In a subset of 63 caste matched samples, DPB1^∗04 was preventive (OR=0.45, CI=0.21-0.95, P=0.036, PF=0.26): the distributions of DRB1^∗1501-DQB1^∗0601-DPB1^∗04 phenotypes were different between patients and controls (P=0.0092). These alleles were predominant in patients and controls of T5SU caste. Conclusion: HLA-DRB1^∗1501 and DQB1^∗0601 predisposed to sputum positive pulmonary tuberculosis, and DPB1^∗04 was preventive and epistatic to this risk. Caste T5SU is an ideal model to study immunology of tuberculosis.