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Asthma and Th2 immunity: The impact of genetic factors and obesity. / Gwyneth Ann Davies

Swansea University Author: Gwyneth Ann Davies

Abstract

Introduction: Th2 immune signalling is key to the pathological substrate of asthma. The primary objective of this thesis was to identify the predictive effects of genetic variants of Th2 signalling at the population level, and to examine interactions between different loci, with relation to asthma a...

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Published: 2007
Institution: Swansea University
Degree level: Doctoral
Degree name: Ph.D
URI: https://cronfa.swan.ac.uk/Record/cronfa42321
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first_indexed 2018-08-02T18:54:25Z
last_indexed 2019-10-21T16:47:36Z
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spelling 2018-08-29T14:35:10.9223380 v2 42321 2018-08-02 Asthma and Th2 immunity: The impact of genetic factors and obesity. db08682cfb0405eb4e9475df60e90b59 NULL Gwyneth Ann Davies Gwyneth Ann Davies true true 2018-08-02 Introduction: Th2 immune signalling is key to the pathological substrate of asthma. The primary objective of this thesis was to identify the predictive effects of genetic variants of Th2 signalling at the population level, and to examine interactions between different loci, with relation to asthma and associated phenotypes. This genetic epidemiological study provided an opportunity to explore also the predictive effects of different measures of obesity on these phenotypes. Methods: An unselected population of 1614 young adults was recruited. Responses to validated questionnaires and spirometry provided clinical and physiological asthma phenotypes. Anthropometry provided the measures of obesity. Assays on venous blood provided immune phenotypes (IgE, eosinophils, eotaxin). Genotyping encompassed 22 polymorphisms in the 1L13, IL4RA and STAT6 genes, representing the Th2 immune signalling pathway. Data analysis used linear and logistic regression models, and a modified regression to address haplotypes. Results: Single polymorphisms and hapiotypes of IL13, IL4RA and STAT6 loci significantly predicted asthma, eczema and hayfever at the population level. Several novel associations were shown for serum IgE levels and airflow obstruction. Significant interaction (epistasis) was identified between variants of IL13 and STAT6 for total IgE levels. Adiposity indices (BMI, waist circumference, body fat) showed consistent associations with asthma and airflow obstruction, but also with Th2 inflammatory markers (IgE, eotaxin and eosinophils) with modulation by sex/smoking status. Conclusions: Genetic variants of Th2 immune signalling are one important source of risk for asthma and allergy in the general population, with variants operating both singly and in combination. Obesity and its causes are also likely to be significant contributors to the occurrence of asthma in the population, and may operate through pro- inflammatory mechanisms. These findings exemplify the polygenic and multifactorial determination of asthma and allergy, through genetic and environmental effects. E-Thesis Immunology.;Epidemiology.;Genetics. 31 12 2007 2007-12-31 COLLEGE NANME Swansea University Medical School COLLEGE CODE Swansea University Doctoral Ph.D 2018-08-29T14:35:10.9223380 2018-08-02T16:24:28.8229868 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Medicine Gwyneth Ann Davies NULL 1 0042321-02082018162445.pdf 10798029.pdf 2018-08-02T16:24:45.2500000 Output 20994963 application/pdf E-Thesis true 2018-08-02T16:24:45.2500000 false
title Asthma and Th2 immunity: The impact of genetic factors and obesity.
spellingShingle Asthma and Th2 immunity: The impact of genetic factors and obesity.
Gwyneth Ann Davies
title_short Asthma and Th2 immunity: The impact of genetic factors and obesity.
title_full Asthma and Th2 immunity: The impact of genetic factors and obesity.
title_fullStr Asthma and Th2 immunity: The impact of genetic factors and obesity.
title_full_unstemmed Asthma and Th2 immunity: The impact of genetic factors and obesity.
title_sort Asthma and Th2 immunity: The impact of genetic factors and obesity.
author_id_str_mv db08682cfb0405eb4e9475df60e90b59
author_id_fullname_str_mv db08682cfb0405eb4e9475df60e90b59_***_Gwyneth Ann Davies
author Gwyneth Ann Davies
author2 Gwyneth Ann Davies
format E-Thesis
publishDate 2007
institution Swansea University
college_str Faculty of Medicine, Health and Life Sciences
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hierarchy_top_id facultyofmedicinehealthandlifesciences
hierarchy_top_title Faculty of Medicine, Health and Life Sciences
hierarchy_parent_id facultyofmedicinehealthandlifesciences
hierarchy_parent_title Faculty of Medicine, Health and Life Sciences
department_str Swansea University Medical School - Medicine{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Medicine
document_store_str 1
active_str 0
description Introduction: Th2 immune signalling is key to the pathological substrate of asthma. The primary objective of this thesis was to identify the predictive effects of genetic variants of Th2 signalling at the population level, and to examine interactions between different loci, with relation to asthma and associated phenotypes. This genetic epidemiological study provided an opportunity to explore also the predictive effects of different measures of obesity on these phenotypes. Methods: An unselected population of 1614 young adults was recruited. Responses to validated questionnaires and spirometry provided clinical and physiological asthma phenotypes. Anthropometry provided the measures of obesity. Assays on venous blood provided immune phenotypes (IgE, eosinophils, eotaxin). Genotyping encompassed 22 polymorphisms in the 1L13, IL4RA and STAT6 genes, representing the Th2 immune signalling pathway. Data analysis used linear and logistic regression models, and a modified regression to address haplotypes. Results: Single polymorphisms and hapiotypes of IL13, IL4RA and STAT6 loci significantly predicted asthma, eczema and hayfever at the population level. Several novel associations were shown for serum IgE levels and airflow obstruction. Significant interaction (epistasis) was identified between variants of IL13 and STAT6 for total IgE levels. Adiposity indices (BMI, waist circumference, body fat) showed consistent associations with asthma and airflow obstruction, but also with Th2 inflammatory markers (IgE, eotaxin and eosinophils) with modulation by sex/smoking status. Conclusions: Genetic variants of Th2 immune signalling are one important source of risk for asthma and allergy in the general population, with variants operating both singly and in combination. Obesity and its causes are also likely to be significant contributors to the occurrence of asthma in the population, and may operate through pro- inflammatory mechanisms. These findings exemplify the polygenic and multifactorial determination of asthma and allergy, through genetic and environmental effects.
published_date 2007-12-31T03:52:44Z
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