Susceptibility to tuberculosis among pulmonary tuberculosis patients: P2X7 and TNF-α gene polymorphisms
Ali Akbar Velayati
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© 2014. Introduction: This study was conducted to assess the rate of human P2X 7 and TNF-α gene polymorphisms among Iranian pulmonary tuberculosis (TB) cases. P2X 7 gene is highly polymorphic, and it is up-regulated by an inflammatory cytokine. Recently, a correlation between the expression of the P2X 7 receptor and the elevated levels of TNF-α have been shown, but the apparent clinical correlation could not be demonstrated. Methodology: This 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 P2X 7 (+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. Results: For 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]). Conclusions: In the studied population, polymorphisms in P2X 7 (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.