Genetic and environmental factors in asthma: a population based European study
Loading...
Document Type
Document Version
Author
Director
Cid Ibeas, Rafael de
Kogevinas, Manolis
Kogevinas, Manolis
Tutor
Other authors
Publication Date
Pages
Embargo date
Citation
Castro Giner, F. Genetic and environmental factors in asthma: a population based European study. Universitat Pompeu Fabra; 2009. handle: http://hdl.handle.net/10803/7194
This citation was generated automatically.
Citation
Doctoral program
Programa de doctorat en Biomedicina
Abstract
L'asma és una malaltia d'etiologia complexa, formada per factors genètics i ambientals, on la interrelació de ambdós factors mitjançant interaccions gen-ambient juga un paper clau. L'objectiu d'aquesta tesi ha sigut aprofundir en el coneixement del paper dels polimorfismes genètics, i la seva interacció amb factors ambientals, en la ocurrència d'asma, atòpia i hiperreactivitat bronquial. Aquest objectiu ha estat desenvolupat a través de la replicació de variants genètiques prèviament identificades, l'avaluació d'interaccions gen-ambient i la identificació de nous gens de susceptibilitat mitjançant un disseny basat en el genotipatge de variants genètiques all llarg del genoma en pools d'ADN. La tesi ha estat majoritàriament duta a terme dins l'estudi European Community Respiratory Health Survey (ECRHS) que està comprès per 5.000 individus seguits durant 9 anys, pels quals es disposa d'un qüestionari complet sobre símptomes respiratoris, avaluacions clíniques, informació sobre exposicions ambientals i mostres de ADN. Aquesta tesi a replicat l'associació del polimorfismes dels gens TNFA i NPSR1 amb asma. A més s'han establert les interaccions entre TNFA i obesitat, NQO1 i contaminació atmosfèrica, i NPSR1 i edat d'inici d'asma. L'anàlisi de pools d' ADN ha permès associar la regió on es situa el gen SGK493 amb atòpia. Aquesta tesi contribueix al coneixement de l'etiologia d'asma amb la identificació i replicació d'associacions genètiques i interaccions gen-ambient.
Asthma is a disease with a complex etiology, involving multiple genetic and environmental factors, and with an important role of the interplay of these factors through gene-environment interactions. In this thesis I aimed to advance our knowledge on the importance of genetic polymorphisms and their interaction with environmental data for the occurrence of asthma and related phenotypes (atopy and bronchial hyperreactivity). This objective was developed through the replication of genetic associations previously reported, the assessment of gene-environment interactions and the identification of new susceptibility genes using genome-wide analysis based on a pooling DNA strategy. The thesis was, mostly, performed within the European Community Respiratory Health Survey (ECRHS). This cohort has information and DNA samples from approximately 5,000 adult subjects followed-up for 9 years, with extensive questionnaires on respiratory symptoms, clinical evaluations and information on environmental exposures. This thesis replicates previous effects on asthma of polymorphisms in TNFA and NPSR1 genes. In addition, interactions have been established between TNFA and obesity, NQO1 and air-pollution, and NPSR1 and age at onset of asthma. The approach based on genome-wide analysis of DNA pools identified the SGK493 region being associated with atopy. This thesis contributes to the understanding of the etiology of asthma through the identification and replication of genetic associations and gene-environment interactions.
Asthma is a disease with a complex etiology, involving multiple genetic and environmental factors, and with an important role of the interplay of these factors through gene-environment interactions. In this thesis I aimed to advance our knowledge on the importance of genetic polymorphisms and their interaction with environmental data for the occurrence of asthma and related phenotypes (atopy and bronchial hyperreactivity). This objective was developed through the replication of genetic associations previously reported, the assessment of gene-environment interactions and the identification of new susceptibility genes using genome-wide analysis based on a pooling DNA strategy. The thesis was, mostly, performed within the European Community Respiratory Health Survey (ECRHS). This cohort has information and DNA samples from approximately 5,000 adult subjects followed-up for 9 years, with extensive questionnaires on respiratory symptoms, clinical evaluations and information on environmental exposures. This thesis replicates previous effects on asthma of polymorphisms in TNFA and NPSR1 genes. In addition, interactions have been established between TNFA and obesity, NQO1 and air-pollution, and NPSR1 and age at onset of asthma. The approach based on genome-wide analysis of DNA pools identified the SGK493 region being associated with atopy. This thesis contributes to the understanding of the etiology of asthma through the identification and replication of genetic associations and gene-environment interactions.
Keywords
gene-environment interaction, environment, genetic polymorphisms, genetic, epidemiology, bronchial hyperreactivity, atopy, asthma, NQO1 - NAD(P)H:quinine oxidoreductase, NPSR1 - Neuropeptide S-Receptor 1, TNFA - Tumor Necrosis Factor Alpha, estrés oxidatiu, edat d'inici d'asma, diòxid de nitrogen, contaminació, obesitat, interaccions gen-ambient, exposicions ambientals, polimorfismes genètics, genètica, epidemiologia, hiperreactivitat bronquial, atòpia, asma, obesity, air-pollution, nitrogen dioxide, age at onset of asthma, oxidative stress, TNFA - Tumor Necrosis Factor Alpha, NPSR1 - Neuropeptide S-Receptor 1, NQO1 - NAD(P)H:quinine oxidoreductase
Subjects
616.2 - Pathology of the respiratory system
Publisher
Universitat Pompeu Fabra
