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 10,000, X2 = 27.07) than controls (F = 404/10,000, 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.