IL-10, TGF-ß, IL-2, IL-12, and IFN-γ Cytokine Gene Polymorphisms in Asthma

Abstract

Asthma is a complex respiratory disease, characterized by airway inflammation and reversible airway obstruction. Both genetic and environmental factors are important in the development and expression of the disease. In order to analyze the genetic profile of Th1 and Th2 cytokines in Iranian asthmatic patients, this study was performed. The allele and genotype frequencies of a number of polymorphic genes coding for IL-10, TGF-beta, IL-2, IL-12, and IFN-gamma were investigated in 60 patients with asthma in comparison with 140 controls. The most frequent genotypes in our patients were IL-10 GA at position-1082 (p = 0.001), IL-10 CT at position -819 (p = 0.001), IL-10 CA at position -592 (p = 0.0001), IL-12 CA at position -1188 (p = 0.003), TGF-beta CG at codon 25 (p = 0.002), IL-2 GT at position -330 (p = 0.004). In contrast, the frequencies of the genotypes IL-10 AA at position -1082 (p = 0.0001) and GG at position -1082 (p = 0.01), IL-10 CC at position -819 (p = 0.001) and TT at position -819 (p = 0.01), TGF-beta TT at codon 10 (p = 0.001), TGF-beta GG at codon 25 (p = 0.005), IL-12 AA at position -1188 (p = 0.004), IL-2 TT at position -330 (p = 0.01) were significantly lower in the patient group. The most frequent haplotypes in the patients were IL-10 GCC (p = 0.008) and ATA (p = 0.0001) at position -1082, -819, -592, and TGF-beta CC (p = 0.036) at codon 10 and codon 25. In contrast, the frequencies of the IL-10 ACC (p = 0.001), TGF-beta TG (p = 0.024), and IL-2 TT (p = 0.001) and GT (p= 0.0001) in the patients were significantly lower than controls. Considering the high frequency of presence of IL-10 ATA haplotype and the IL-2 GT genotype, it seems that the production of IL-10 and IL-2 in the asthmatic patients could be lower than normal subjects.

PRMT1 Upregulated by Epithelial Proinflammatory Cytokines Participates in COX2 Expression in Fibroblasts and Chronic Antigen-Induced Pulmonary Inflammation

“…Redington et al (12) also reported that TGF-b levels were increased in bronchoalveolar lavage fluid of asthma patients after segmental allergen challenge. Similarly, other studies confirmed that epithelial cells from asthma patients released higher levels of TGF-b than did epithelial cells obtained from nonasthma subjects (13,14). Furthermore, TGF-b expression correlated with the degree of subepithelial fibrosis and was significantly increased in subjects with severe asthma and associated eosinophilia (15).…”

Meta-analysis of the IL-10 promoter polymorphisms and pediatric asthma susceptibility

“…The studies were excluded for the following reasons: reviews (N = 5), duplicated data (N = 3), non-case-control study (N = 5), no useful data (N = 2), irrelevant to pediatric asthma (N = 12). Finally, a total of 16 case-control studies comprising 2494 cases and 2160 controls were included in this meta-analysis to evaluate the association between IL-10 promoter polymorphisms and the risk of pediatric asthma (Zhang et al, 2002;Schubert et al, 2006;Li et al, 2006Li et al, , 2007Movahedi et al, 2008;Zedan et al, 2008;Undarmaa et al, 2010;Hussein et al, 2011;Kim et al, 2011;Wei et al, 2011;Xie, 2012;Ji et al, 2013;Smolnikova et al, 2013;Tan et al, 2013;Hussein et al, 2014;Xu et al, 2014). Eleven of the studies were performed in an Asian population, and three and two of the remaining studies were conducted in people of African and Caucasian descent, respectively.…”

“…The -592C/A polymorphism in the IL-10 promoter has been reported to influence the expression of IL-10 in the serum, which suggests the importance of polymorphisms in the IL-10 promoter region in the pathogenesis of asthma (Ji et al, 2013). Previous studies have indicated that these polymorphisms might be associated with increased susceptibility to asthma (Movahedi et al, 2008;Zedan et al, 2008). For instance, Zedan et al (2008) reported that the GG genotype at the IL-10 -1082 region could be a contributing factor for the increased susceptibility to, and severity of, childhood asthma in Egypt.…”

“…Xu et al (2014) reported a similar finding in a Chinese population. Moreover, Movahedi et al (2008) reported a significant association between the IL-10 -1082G/A, -819C/T, and -592C/A polymorphisms and pediatric asthma in Iran. In contrast, other studies have reported no significant association between these variants and the risk of pediatric asthma; for example, Kim et al (2011) revealed that the IL-10 -1082G/A, -819C/ T, and -592C/A polymorphisms were not associated with pediatric asthma in a Korean population, which was consistent with the results obtained by Li et al (2007).…”

The Role of DNA Methylation in Common Skeletal Disorders

“…Asthma is a complex disease known to be influenced by both genetic and environmental factors [8][9][10][11][12][13][14][15][16]. 26.7 million or about 9.7% of the population in the United States have had asthma during their lifetime [17].…”