Susceptibility to and severity of tuberculosis is genetically controlled by human leukocyte antigens

OBJECTIVE: To assess the role of HLA polymorphism in the susceptibility to tuberculosis in Syria.

METHODS: We used the polymerase chain reaction with sequence specific primer method to study the DRB1* locus in 147 Syrian patients with positive sputum smear or sputum culture for Mycobacterium Tuberculosis strains, and 209 Syrian healthy matching individuals with negative tuberculin skin test. Patients were randomly recruited from the Damascus Health Center of Tuberculosis and Pulmonary Diseases during 2005-2007. The study was carried out at the Laboratory for Research and Genetic Consultations, in the Faculty of Medicine of Damascus University, Damascus, Syria.

RESULTS: A significant decrease of the DRB1*11 allele was observed in patients compared to controls (34.7% in patients versus 51% in control, odds ratio [OR]=0.51, p=0.003, corrected p=0.04), whereas the DRB1*04 allele was increased in patients (38.8% in patients versus 26.4% in controls, OR=1.77, p=0.01, corrected p>0.05). This increase became significant when individuals with the DRB1*11 allele were removed from both patients and controls (33% in DRB1*11 negative patients versus 17% in DRB1*11 negative controls, OR=2.5, p=0.003, corrected p=0.03). In addition, pulmonary cavitation was significantly increased in the DRB1*04 positive patients compared to patients without the DRB1*04 allele (33% in DRB1*04 positive patients versus 16% in DRB1*04 negative patients, OR=2.7, p=0.04).

CONCLUSION: The DRB1*04 allele is associated with susceptibility to pulmonary tuberculosis, whereas DRB1*11 is associated with protection from pulmonary tuberculosis in the Syrian population. In addition, cavity formation in patients with pulmonary tuberculosis seems to be favored by presence of the DRB1*04 allele.