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

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.