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 "CCGGGGGGCCAA" 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.

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