Revised: March 3, 2013
Accepted: March 16, 2013
Published online: March 28, 2013
Processing time: 110 Days and 1.8 Hours
AIM: To characterize cytokine gene polymorphisms in patients with idiopathic pulmonary fibrosis (IPF) compared to healthy controls.
METHODS: Fifty-six IPF patients were involved in the study. The control population consisted of 144 healthy volunteers without history of lung disease. All of the patients were diagnosed with IPF according to the American Thoracic Society/European Respiratory Society consensus statement. Polymorphisms in the interleukin (IL)-1, IL-1, IL-1R, IL-1RA, IL-2, IL-4, IL-6, IL-10, IL-12, tumour necrosis factor, interferon, transforming growth factor, IL-1, IL-2, IL-4 and IL-4RA genes were characterized by polymerase chain reaction with sequence-specific primers. Statistical analysis was performed using the MedCalc statistical software. A Bonferroni correction of significance at an alpha of 0.05 was used for multiple analyses. A corrected P value less than 0.0023 (0.05/22) was considered significant.
RESULTS: We found significant differences in the IL-4 promoter region polymorphisms between IPF patients and controls. Namely, polymorphisms of IL-4 (-590) [computed tomography (CT) in 32 of 56 patients vs 27 of 144 controls; P < 0.0001] and IL-4 (-33) (CT in 25 of 56 patients vs 27 of 144 controls; P = 0.0006) differed between both groups. With regard to haplotypes, we found differences in the frequencies for haplotype 1 of IL-4 (-1098) (-590) (-33) between IPF and controls (TCC in 23 of 56, TTC in 10 of 56, and TTT in 21 of 56 patients vs TCC in 112 of 144, TTC in 0 of 144, and TTT in 32 of 144 controls; P < 0.0001). We did not find significant differences in gene polymorphism frequencies of other cytokines in the IPF group vs the controls.
CONCLUSION: We hypothesize that IL-4 promoter polymorphisms could be involved in the pathogenesis of IPF, likely via enhancement of the Th2 cytokine milieu with exaggerated fibroproliferative healing.
Core tip: Enhanced fibroproliferation resulting in terminal fibrosis is the main feature of idiopathic pulmonary fibrosis (IPF). Various mechanisms of alveolar damage and its healing are involved in IPF development. One of the potential contributing pathogenic factors is the genetically encoded imbalance of cytokine production. We found differences between the frequencies of interleukin (IL)-4 gene promoter polymorphisms in IPF patients vs controls. Based on these results and on the observation that IL-4 promoter polymorphisms can influence IL-4 production, we hypothesize that IL-4 promoter polymorphisms could be involved in the pathogenesis of IPF, likely by enhancing the Th2 cytokine milieu with subsequent fibroproliferative healing.