Proinflammatory Cytokine Gene Polymorphisms among Iranian Patients with Asthma

Abstract

Asthma is one of the most common respiratory diseases caused by acute and chronic inflammation of airways. Proinflammatory cytokines could contribute to this inflammatory process. This study was performed in order to analyze the genetic profile of proinflammatory cytokines in Iranian asthmatic patients. The allele and genotype frequencies of a number polymorphic genes coding for tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 alpha, IL-1 beta, IL-1 receptor (IL-1R), IL-1RA, and IL-6 were investigated in 60 patients with asthma in comparison with 140 controls using polymerase chain reaction with sequence-specific primers. The most frequent genotypes in our patients were TNF-alpha GA at position -308 (P = 0.001), TNF-alpha AA at position -238 (P = 0.01), IL-1 alpha TC at position -889 (P = 0.0001), IL-1 beta TC at position -511 (P = 0.0001), and IL-1RA TC at position Mspa-I 11100 (P = 0.001). In contrast, the frequencies of the genotypes TNF-alpha GG at position -308 (P = 0.001), IL-1 alpha CC at position -889 (P = 0.005), IL-1 beta CC at position -511 (P = 0.0001), and IL-1RA TT at position Mspa-I 11100 (P = 0.0001) in the patient group were significantly lower than controls. The most frequent haplotypes for TNF-alpha (positions 308, -238) was A/A in the patient group in comparison with controls (P = 0.0001). While environmental factors are important in the development of asthma, genetic factors could have a critical role in the expression of the disease. Considering the high frequency of presence of TNF-alpha AG genotype (-308), it seems that the production of TNF-alpha in the asthmatic patients could be higher than normal subjects.