Polymorphisms of Interleukin 13 (IL13) in Local Asthmatic Population

Abstract

Asthma is a chronic inflammatory disorder characterized by wheezing, breathlessness, chest tightness and cough. The inflammation is responsible for bronchial hyperresponsiveness which renders the patient susceptible to certain environmental stimuli. The environmental factors alone are not responsible for these changes as they have an intricate interaction with genetic factors. In this study we determined the spectrum of symptoms and their correlation with serum IgE levels in asthmatic patients since no such data could be found for indigenous population. Cortisol and ACTH levels were determined to ascertain the status of hypothalamic pituitary adrenal axis. Interleukin 13 gene polymorphisms and their association with asthma and serum IgE levels were investigated. For the present study a detailed history was taken and peak expiratory flow measured on 164 asthmatic and 50 controls. Seventy five randomly selected patients underwent serology and SNP genotyping. Serum was analyzed for total IgE, cortisol and ACTH levels. Six SNPs of interleukin 13 gene were studied by PCR-RFLP. Four polymorphisms were from the promoter region C-1512A, T-1112C, A-646G and C-469T, one nonsynonymous polymorphism from the exon 4 A2044 G (Arg to Gln) and a 3’UTR polymorphism A2525G. The results of this research revealed that majority of patients belonged to moderate intermittent to severe persistent group. Exposure to dust was the most common triggering factor in our population. Serum IgE levels were directly proportional to the severity of asthma and were significantly correlated with history of allergy. However, no correlation was found between IgE levels and family history of asthma. Adrenal functions were © Dr Afia Hasnain 2008 xviiPhD Thesis Dr Afia Hasnain normal when compared with the control group. Two SNPs T-1112C and A2044G showed strong association with serum IgE levels and both the presence and the severity of asthma. C-1512A showed association with asthma and its severity and was the only polymorphism that showed an association with the family history of asthma. While A2525G had a weak association with serum IgE levels only. The other two polymorphisms were in very low frequency in our population and hence no association with phenotypes could be ascertained. It could be concluded from the present investigation that exposure to dust could be the most common precipitating factor of asthma in our population. The two previously studied SNPs T-1112C and A2044G are strongly associated with serum IgE levels and both presence and severity of asthma in our population sample.