Susceptibility to tuberculosis among pulmonary tuberculosis patients: P2X7 and TNF-α gene polymorphisms

AbstractIntroductionThis study was conducted to assess the rate of human P2X7 and TNF-α gene polymorphisms among Iranian pulmonary tuberculosis (TB) cases. P2X7 gene is highly polymorphic, and it is up-regulated by an inflammatory cytokine. Recently, a correlation between the expression of the P2X7 receptor and the elevated levels of TNF-α have been shown, but the apparent clinical correlation could not be demonstrated.MethodologyThis study included 80 confirmed pulmonary tuberculosis (PTB) cases. Fifty control subjects were selected from the TB patients (clinical and laboratory) who had positive tuberculin tests (10–15mm) and showed no sign of diseases (laboratory, radiological and clinical parameter). Single nucleotide polymorphisms (SNPs) in P2X7 (+1513, −762) and TNF-α (at −238, −308, −244, −857, −863) genes were assessed using PCR-RFLP and allele-specific PCR. Thereafter, haplotype and diplotype variability were compared and analyzed.ResultsFor 1513 loci, the heterozygosity was higher in patients (35%; 44.3%) than control subjects (12%; 24%) [(p=0.026) ORS; 2.45 CI 95% (1.13–5.33)]. For −762 loci, the frequency of mutant alleles between patients and controls were not statistically significant. No statistical difference was observed in allele frequencies of TNF −308 and −857. However, the frequency of −238 allele were more in TB cases (72.1%) (P=0.000)[ORs: 5.85(2.70–12.64). Data analysis showed more frequencies of haplotypes, i.e., TGGA-CA and CGGA-TA in patients (21.5%; 14.6%) than the control group (2.0%; 6.0%), respectively. Additionally, the diplotype “CCGGGGGG-CCAA” was significantly associated with susceptibility to PTB (1.9 [0.08–48.3]).ConclusionsIn the studied population, polymorphisms in P2X7 (1513) and TNF-α (−238) gene was associated with the risk of developing PTB. Additionally, distribution of haplotype and diplotype variables did appear to be more specific than SNPs