Abstract: Objective To investigate the relationship between the HLA-DRB1 gene polymorphisms and susceptibility to pulmonary tuberculosis (PTB) in Han nationality of Tangshan city. Methods 1∶1 matched case-control study was adopted (in March to early June in 2010 in Tangshan TB hospitals), 124 new adult TB patients of Han nationality (age 18 and above) were enrolled consecutively as case group. Three hundred and sixty-one health people infected with Mycobacterium tuberculosis confirmed by the unified tuberculin test (PPD) in the physical examination, with the same nationality, same sex, similar age (age difference was less than 3 years), and same residence matching conditions, were selected at the same period. Each case had at least 2 people matched, in which 1 was randomly selected to match the case. One hundred and twenty-four people were randomly selected among 361 people as control group. Polymerase chain reaction-sequence-specific primers technique (PCR-SSP) and restriction fragment length polymorphism (RFLP) were used to type polymorphisms (DR15, DR16, DR1 and DR11). Information on environmental-related risk factors and pathological changes of TB was collected using a pre-tested standard questionnaire. Univariate and multivariate conditional logistic analysis were conducted using SPSS 12.0. Results DR11 wild type accounted for 85.5% (106/124) in case group and 87.1% (108/124) in control group, without statistical significance (P=0.712, OR=1.146, 95%CI＝0.555-2.366). Cases with DR16 wild type was 75.0% (93/124), and was 83.1% (103/124) in control group, there was no statistical significance (P=0.119, OR=1.635, 95%CI＝0.879-3.042)). Cases with DR15 wild type accounted for 85.3% (81/124), and 82.2% (102/124) in control group had this wild type, which was statistically lower than that in case group (P=0.002, OR=2.461, 95%CI＝1.363-4.444). According to the above results, DR15 gene mutation might be the susceptible genotype of PTB. If DR15 genetic mutation and DR16 genetic mutation occurred together, the risk of PTB increased (P=0.007, OR=4.904, 95%CI=1.554-15.476), which was significantly higher than any mutation, so that DR15 and DR16 has synergistic effects on PTB susceptibility. Univariate analysis was conducted for 17 environmental factors. In multivariate analysis, associations of TB and DR15 genotype still remained adjusting for scar of BCG, BMI, per capita living space and family history (Waldχ²=9.844,P=0.002, OR=2.996, 95%CI=1.510-5.945). Conclusion DR15 gene mutant might affect the susceptibility to TB in Han nationality in Tangshan city.

Key words: Tuberculosis, pulmonary/genetics, HLA-DRB1 chains, Polymorphism, genetic, Genetic predisposition to disease, Case-control studies