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Title of Thesis

Polymorphisms of Interleukin 13 (IL13) in Local Asthmatic Population

Author(s)

Dr Afia Hasnain

Institute/University/Department Details
Department Of Physiology And Cell Biology / University Of Health Sciences, Lahore
Session
2008
Subject
Physiology And Cell Biology
Number of Pages
134
Keywords (Extracted from title, table of contents and abstract of thesis)
Asthma, Chronic, Breathlessness, Inflammation, Serum, Polymorphisms, Lnterleukin, Asthmatic, Population, Severity, Genotyping

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 toGln) 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 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.

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1,292 KB
S. No. Chapter Title of the Chapters Page Size (KB)
1 0 CONTENTS
 

 

ix
61 KB
2 1 INTRODUCTION

1.1 Epidemiology
1.2 Immunoglobulin E in asthma
1.3 Hypothalamic Pituitary Adrenal Axis in asthmatics
1.4 Role of Cytokines in Asthma
1.5 Interleukin 13

1
93 KB
3 2 LITERATURE REVIEW


2.1 Asthma
2.2 Epidemiology of Asthma
2.3 Serum IgE levels in Asthma
2.4 Hypothalamic Pituitary Adrenal Axis in Asthma
2.5 Genetics of Asthma
2.6 Role of IL-13
2.7 Interleukin 13 gene Polymorphisms

7
133 KB
4 3 MATERIAL AND METHODS


3.1 Study Population
3.2 Sample Collection
3.3 Serology
3.4 Genotyping of IL-13 Polymorphisms
3.5 Statistical Analysis

41
783 KB
5 4 RESULTS

4.1 Characteristics of Population Sample
4.2 Serology
4.3 Association of IL-13 SNPs with asthma

62
218 KB
6 5 DISCUSSION

 

86
85 KB
7 6 CONCLUSIONS

 

94
56 KB
8 7 APPENDICES AND REFERENCES

 

95
142 KB