Cytotoxic T-Lymphocyte Antigen-4 (CTLA-4) Gene Polymorphism is Associated with Pulmonary Tuberculosis Susceptibility in a Thai Population

Cytotoxic T lymphocyte antigen-4 (CTLA-4) is a T-cell inactivation receptor and has been found to be elevated in Tuberculosis (TB) patients. The functional polymorphisms in CTLA-4 gene, including CTLA4+49A/G (rs231775) and CTLA-4+6230A/G (rs3087243) have been reported to be associated with the risk for many diseases. The two aforementioned functional polymorphisms in the CTLA-4 gene were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in order to investigate the possible susceptibility to pulmonary TB (PTB) in a Thai population. In this study, TB patients were grouped as 1) PTB with and without comorbidity of other diseases (PTB) 2) PTB without comorbidity of other diseases (PTBWO) 3) PTB comorbidity with other diseases (PTBD). We demonstrated that the allele frequency of CTLA-4+49A was higher in PTB, PTBWO, and PTBD groups than in healthy controls subjects (HCS), but no significant association of CTLA-4+49A/G polymorphisms with PTB, PTBWO and PTBD were seen. Whereas the CTLA-4+6230A allele was significantly higher in PTB, PTBWO and PTBD groups than in HCS, and the CTLA-4+6230A allele was found to be significantly associated with PTB, PTBWO and PTBD (P=0.007, OR 2.111, 95%CI(1.220-3.652); P=0.0218, OR 2, 95%CI(1.100-635); P=0.0439, OR 2.5, 95%CI(1.004-6.227) for PTB, PTBWO and PTBD respectively), as well as CTLA-4+6230AG genotype was found to be significantly associated with PTB and PTBWO (P=0.0432, OR 2.259, 95%CI(1.018-5.014); P=0.0392, OR 2.464, 95%CI(1.034-5.874) for PTB and PTBWO respectively). For the combination of CTLA-4+49A/G+6230A/G genotypes, +49AA+6230AA and +49AG+6230AG genotypes was more frequent in PTB and PTBWO groups. This study is the first to investigate CTLA-4+49A/G and +6230A/G polymorphisms in PTB patients in Thailand, The A allele and AG genotype of CTLA-4+6230A/G was significantly associated with PTB, suggesting a possible genetic influence on TB susceptibility. These findings indicate that CTLA-4 polymorphisms, especially CTLA4+6230A/G, may play a role in PTB risk in the Thai population.