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The purinergic P2X 7 -receptors and tumor necrosis factor-alpha (TNF-α) may play important roles in the development of pulmonary tuberculosis (PTB). Genetic contribution of the host is among the most important factors that plays a significant role in the susceptibility of the disease. In this regard, both genes for P2X 7 receptor and TNF-α have been identified as essential components of the host immune response in the containment of TB. However, the relationship between P2X 7 and TNF-α polymorphism and TB susceptibility remains inconclusive. Objectives: This study was designed to investigate the association of P2X 7 and TNF- α gene polymorphisms among Iranian PTB patients. Materials and Methods: In a case-control study, single nucleotide polymorphisms (SNPs) in P2X 7 (+1513, -762) and TNF-α (at -238, -308, -244, -857 and -863) genes were assessed using PCR-RFLP and allele-specific PCR. Thereafter, haplotype and diplotype variability were compared and analyzed. Results: For the 1513 loci, the heterozygosity was higher in patients (35; 44.3%) than control subjects (12; 24%) ((P = 0.026) ORS; 2.45 CI95 % (1.13 - 5.33)). For the -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 A allele was more in tuberculosis (TB) cases (72.1%) (P = 0.000) (ORs: 5.85 (2.70 - 12.64)). Data analysis showed greater frequency of haplotypes, i.e. TGGA-CA and CGGA-TA in the patient (21.5%; 14.6%) than control group (2.0%; 6.0%), respectively. Additionally, the diplotype "CCCCAA" 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 (S-238) gene were associated with risk of developing PTB. Additionally, distribution of haplotype and diplotype variables did appear to be more specific than SNPs.

Association of Receptors, Purinergic P2X7 and Tumor Necrosis Factor-alpha Gene Polymorphisms in Susceptibility to Tuberculosis Among Iranian Patients