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Asthma as a chronic inflammatory airway disease is considered to be the most common chronic disease that is involving genetic and environmental factors. Toll like receptors (TLRs) and other inflammatory mediators are important in modulation of inflammation. In this study, we evaluated the role of TLR2 Arg753Gln and TLR4 Asp299Gly polymorphisms in the asthma susceptibility, progress, control levels and lung functions in Iranian patients. On 99 asthmatic patients and 120 normal subjects, TLR2 Arg753Gln and TLR4 Asp299Gly polymorphisms were evaluated by PCR-RFLP method recruiting Msp1 and Nco1 restriction enzymes, respectively. IgE serum levels by ELISA technique were determined and asthma diagnosis, treatment and control levels were considered using standard schemes and criteria. Our results indicated that the genotype and allele frequencies of the TLR2 Arg753Gln and TLR4 Asp299Gly polymorphisms were not significantly different between control subjects and asthmatics and were not related to in asthma features such as IgE levels, asthma history and pulmonary factors. Wherease some previous studies indicated TLRs and their polymorphisms might have some role in asthma incidence and features, our data demonstrated that TLR2 Arg753Gln and TLR4 Asp299Gly gene variants were not risk factors for asthma or its features in Iranian patients. Genetic complexity, ethnicity, influence of other genes or polymorphisms may overcome these polymorphisms in our asthmatics.

Asthma is a multifactor inflammatory disorder, and its management requires understanding of its various pathogenesis and control mechanisms. Cytokines and other inflammatory mediators are important factors in asthma pathophysiology. In this study, we evaluated the role of cytokine polymorphisms in the asthma susceptibility, progress, control, and lung functions. IL-4-C590T polymorphism by PCR-RFLP method, IFN-γ T+874A, TNF-α-A308G, IL-6 G-174C and TGF-β T+869C variants by ARMS-PCR method and IgE serum level by ELISA technique were determined in 81 asthmatic patients and 124 normal subjects. Asthma diagnosis, treatment and control levels were considered using standard schemes and criteria. TNF-α-308GA genotype was more frequent in asthmatics (P = 0.025, OR 3.352), and polymorphisms between different asthma control levels (P > 0.05) were not different. IFN-γ+874AT genotype had a positive correlation with the familial history of asthma (P = 0.034, OR 2.688). IL-6-174C allele (P = 0.045), TNF-α-308GG genotype (P = 0.002) and TNF-α-308G allele (P = 0.004) showed reduced values, and TNF-α-308GA genotype (P = 0.002) increased FEF25-75 value in asthmatics. IFN-γ+874AA genotype caused a decrease in FVC factor (P = 0.045). This study showed that TNF-α-308GA is a risk factor for asthma, but cytokine gene variants do not affect asthma control and IgE serum levels. Variants producing lower levels of IL-6, TNF-α and IFN-γ are associated with reduced pulmonary capacities. To achieve an appropriate schema for asthma management, further studies with consideration of different aspects in a larger group of patients would be more elucidative.

Background: Chemokines and their receptors are clinically important mediators, as the chemokine receptors are expressed on almost all immune cells. They play pivotal roles in pathogenesis of almost all clinical situations including asthma. Correspondingly, MIP-1α (CCL3), MIP-1β (CCL4), and RANTES (CCL5) are among the important chemokines involved in the pathogenesis of asthma. These chemokines bind to the CCR5 (their related receptor) on the cell surfaces. Attachment of related chemokine ligands to CCR5 plays an important role in the pathogenesis of asthma; hence, this study aimed to analyze δ32 mutations in CCR5 in asthmatic patients., Material and Methods: This experimental study was undertaken on 162 asthmatic patients and 200 healthy controls during February to June 2008 at Rafsanjan University of Medical Sciences. The Gap-PCR method was applied to analyze the δ32 mutation in the CCR5 gene, and demographic data (eg, age, sex, occupation, socio-economic status) were collected using a questionnaire., Results: The findings of this study indicated that none of the asthmatic patients exhibited δ32 mutation in CCR5 chemokine receptor while only 3 (1.5%) of controls had the heterozygotic form of this mutation., Discussion: Several research groups analyzed δ32 mutations in CCR5 in different diseases, including asthma. Some investigations reported a significant relation between asthma and δ32 mutations in CCR5, but there are also many reports which failed to find a relation between asthma and this mutation. Based on the results of this study and others, it seems that the δ32 mutation does not affect the pathogenesis of asthma.