Association of human leukocyte antigen DRB1 polymorphism and tuberculosis: a meta-analysis

OBJECTIVE: To determine whether the human leukocyte antigen DRB1 (HLA-DRB1) is associated with clinical tuberculosis (TB). METHODS: Pooled odds ratios (OR) with 95% confidence intervals (CIs) were used to evaluate the strength of the association between HLA-DRB1 alleles and risk of TB. The x(2)-based Q-test and I-2 statistics were calculated to examine heterogeneity. Egger's test was performed for the assessment of publication bias. Subgroup analysis was performed based on ethnicity and genotyping methods. RESULTS: A total of 19 case-control studies with 16 alleles (HLA-DRB1*01-HLA-DRB1*16) were included in this meta-analysis. No significant publication bias was detected among these studies. The HLA-DRB1*03 (OR 0.77, 95%CI 0.64-0.93, P = 0.0057) showed a protective effect, while HLA-DRB1*04 (OR 1.24, 95%CI 1.00-1.55, P = 0.0494), HLA-DRB1*08 (OR 1.45, 95%CI 1.14-1.86, P = 0.0030) and HLA-DRB1*16 (OR 1.39, 95%CI 1.04-1.87, P = 0.0269) were significantly associated with increased TB occurrence. Subgroup analysis showed that both ethnicity and genotyping method affected the association between HLA-DRB1*03, HLA-DRB1*04 and HLA-DRB1*08 alleles and TB occurrence. CONCLUSION: These results reinforce the importance of HLA-DRB1 alleles in the development of infectious diseases.