Association of Receptors, Purinergic P2X7 and Tumor Necrosis Factor-Alpha Gene Polymorphisms in Susceptibility to Tuberculosis Among Iranian Patients
IntroductionThe purinergic P2X7-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 P2X7 receptor and TNF-α have been identified as essential components of the host immune response in the containment of TB. However, the relationship between P2X7 and TNF-α polymorphism and TB susceptibility remains inconclusive..
ObjectivesThis study was designed to investigate the association of P2X7 and TNF- α gene polymorphisms among Iranian PTB patients..
Materials And MethodsIn a case-control study, single nucleotide polymorphisms (SNPs) in P2X7 (+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..
ResultsFor 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)]..
ConclusionsIn the studied population, polymorphisms in P2X7 (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..
Archives of Clinical Infectious Diseases, Volume:8 Issue:3, 2014
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