Asthma is a multifactor chronic inflammatory disorder of the airways and a variety of genetic and environmental factors contribute to its pathogenesis. Immune and inflammatory elements are important factors in induction, progress and clinical outcomes of asthma.
Toll like receptors (TLRs) are family of transmembrane proteins involved in innate immunity and pathogen recognition. TLRs are highly polymorphic, and play an important role in both innate and adaptive immunity.
There is potential role of TLRs pathway in the overall immune reconstitution, So variation within genes of TLRs are associated with altered immune response which may be associated with asthma and atopic sensitization.
The aim of the present study was to study the association between single nucleotide polymorphism in genes of TLR2 and TLR4 and the risk of bronchial asthma.
This study was carried out on 40 patients (24 males and 16 females) suffering from bronchial asthma and 20 healthy subjects (12 males and 8 females) as a control group. The patients were chosen from Chest Department of Benha University Hospital.
The age of the studied asthmatic cases ranged from 30-60 years. The control subjects were chosen to be age and sex matched with the asthmatic patients. The study was done at Medical Microbiology and Immunology Department of Benha Faculty of Medicine.
Sixty five (65%) of studied asthmatic cases had +ve family history of asthma or other allergic diseases like allergic rhinitis and were atopic (giving positive intradermal skin test), while only 15% of control subjects had +ve family history of asthma or other allergic diseases and were atopic.
Blood samples were collected from asthmatic patients and control subjects for detection of TLR2 & TLR4 gene polymorphism using polymerase chain reaction- Restriction Fragment Length Polymorphism. (PCR - RFLP).
PCR-RFLP detected three genotypes of TLR2 gene at 753 position : GG normal genotypes in 12 cases (30%), AG heterogenicity in 25 cases (62.5%) and AA homogenicity in 3 cases (7.5%) indicating strong association between AG polymorphism of TLR2 at 753 position and the risk of the bronchial asthma.
PCR-RFLP also detected three genotypes of TLR4 gene at 299 position : AA normal genotypes in 8 cases (20%), AG heterogenicity in 26 cases (65%) and GG homogenicity in 6 cases (15%) indicating strong association between AG polymorphism of TLR4 at 299 position and the risk of the bronchial asthma.
The A allele of TLR2 and G allele of TLR4 was significantly increased in asthmatic cases than in control group.
From this study we can conclude that for TLR2 (Arg753Gln) G>A, the major G allele was significantly associated with a decreased asthma risk. For TLR4 (Asp299Gly) A>G, the AA homozygote genotype and A allele tended to be associated with a decreased asthma risk. These results implicate that the major allele in TLR polymorphisms might be generally associated with a protective effect
There were insignificant correlation between the three TLR genotypes (AA, AG, GG) and sex, smoking, family history and atopy (+ve intradermal skin test).
It may therefore be concluded that PCR-RFLP technique targeting the TLR2& TLR4 gene is considered an important standard for detection of people at risk for bronchial asthma.
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