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ASSOCIATION OF TAP1 AND TAP2 GENE POLYMORPHISMS WITH TUBERCULOSIS IN KOREANS.
E.Y. Roh, M.D., M.H. Park, M.D., J.A. Yoon, M.Y. Kim, S.Y. Kwon, M.D., J.J. Yim, M.D., S.K. Han, M.D. and Y.S. Shim, M.D.. Seoul National University College of Medicine Department of Laboratory Medicine and Seoul Korea, Seoul National University College of Medicine, Department of Internal Medicine.

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It has been estimated that only 10% of persons infected with M. tuberculosis will ever develop clinical disease, and genetic variability is thought to be an important modulator of tuberculosis susceptibility. TAP gene products are involved in the processing of endogenous peptides that bind to HLA class I molecules, and TAP1-deficient mice have been shown to be markedly susceptible to infection with M. tuberculosis. We have investigated TAP1 and TAP2 gene polymorphisms in 219 Korean patients with pulmonary tuberculosis (PTB) and 210 healthy controls using PCR-RFLP method. Frequencies of TAP1 gene were not significantly different between patients and controls. Analysis of TAP2 gene polymorphism (TAP2*A1, A2, B, Bky2, C, D, E, F, G, H) revealed a significantly increased frequency of the phenotype TAP2*Bky2, *C, or *E in PTB patients as compared to controls (50.2% vs. 30.5%, OR=2.30, p = 0.00005). We previously reported that HLA-DRB1*0803 is associated with genetic susceptibility to PTB in Koreans, especially with disease severity and drug resistance. Further analysis on the TAP2 gene polymorphism among DRB1*0803-negative subjects also showed a significantly increased frequency of TAP2*Bky2, *C, or *E in PTB patients as compared to controls (40.8% vs. 22.4%, OR=2.40, p = 0.002). TAP2 gene polymorphism was not associated with disease severity or drug resistance of tuberculosis. Our results suggest that TAP-dependent peptide antigen presentation plays an important role in immunity to tuberculosis, and individuals carrying TAP2*Bky2, *C or *E alleles are more susceptible to PTB.