Cytokines Genes Polymorphisms in Iranian Patients with Pulmonary Tuberculosis

Background: Pulmonary tuberculosis (PTB) has recently become a major problem in developed countries especially in immune compromised HIV infected individuals. Cytokines, their genes and receptors have been implicated in the protective immunity, pathophysiology and development of tuberculosis.   Material & Methods: In the present study the genotype frequencies of a number of polymorphic genes coding for cytokines or for cytokine receptors have been investigated in a case control study including a group of 40 Iranian PTB patients and 40 healthy individuals. The allelic polymorphism of cytokines SNPs were analyzed according to the protocols of the cytokine component designed for the 13th IHW by the Heidelberg University group. Using PCR-SSP method the following cytokine genes have been determined: IL-1   ¿ (T/C –889), IL-1¾ (C/T +3962), IL-1R (C/T pstI 1970), IL-1RA ( T/C mspaI 1100), IL-4RA (G/A +1902), IL- 12 (C/A –1188), TGF-   ¾ (C/T codon 10, G/C codon 25), TNF-¿ (G/A –308, G/A –238), IL-2 (T/G –330 G/T +166), IL-4 (T/G –1098, T/C –590, T/C –33), IL-6 (G/C –174, G/A nt 560), IL-10 (G/A –1082, C/T –819, C/A –592).   Results: From IL-1R cluster (pro- inflammatory cytokines) a positive significant association was found at position pstI 1970 C/T polymorphism where the C allele was over presented in the PTB patients (60% vs. 37.5%, P = 0.04). A significant negative association at codon 10 TGF-   ¾ C/T polymorphism has also been shown in our patients, where the T allele was not detected in the patients but 10% of the control subjects expressed this allele (Fisher exact test, P = 0.05). At this codon allele T (Leucine substitution) is associated with high TGF-   ¾ production. For TNF   ¿ an insignificant tendency was found at position -308 A/G polymorphism where the G allele carried by 80% of cases and 65% of controls (P = 0.07). At position -238 a negative association was found at the GA polymorphism (10% vs. 25%, P = 0.07). For IL-6 an insignificant positive association at position -174 C/G polymorphism, G allele (57.5% vs. 37.5, P = 0.07) was found. At the other cytokine genes no specific association were found.   Conclusion: In conclusion it is suggested that C allele at position pstI 1970 of IL-1 cluster increases and T allele at codon 10 of TGF-   ¾ decreases in PTB patients.