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Gene-environment interactions in the Etiology of Chronic Obstructive Pulmonary Disease (COPD); the SAPALDIA Biobank

English title Gene-environment interactions in the Etiology of Chronic Obstructive Pulmonary Disease (COPD); the SAPALDIA Biobank
Applicant Probst-Hensch Nicole
Number 123171
Funding scheme ProDoc
Research institution Institut für Sozial- und Präventivmedizin Universität Basel Swiss TPH
Institution of higher education University of Basel - BS
Main discipline Genetics
Start/End 01.10.2008 - 30.09.2011
Approved amount 159'417.00
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All Disciplines (3)

Discipline
Genetics
Respiratory Diseases
Methods of Epidemiology and Preventive Medicine

Keywords (4)

COPD; air pollution; gene-environment interactions; SAPALDIA

Lay Summary (English)

Lead
Lay summary
Lead
Chronic obstructive pulmonary disease (COPD) causes high costs and suffering worldwide. The project investigates interactions between genes and noxious exposures underlying development of COPD. Understanding the causes of COPD has the potential to suggest new and cost-effective preventive measures.

Background
COPD is an inflammatory disease of the lung associated with progressive, irreversible narrowing of the airways and entails substantial costs. The inflammatory processes arise from the combined impact of noxious substances in the air (such as tobacco smoke or air pollution) and underlying genetic susceptibility. Genetic variation affects the disese risk on two major tracks: by reducing the capacity of the body to handle noxious exposures and by hampering mechanisms which protect body structures from destructive side effects of inflammation. This complex interplay between genes and the environment in the development of COPD has not been extensively researched yet. But it is probably of major importance for disease causation, as until now, apart from smoking no other major risk factor could be identified.

Specific Aim
The goal of the project is to identify important mechanisms of interaction between noxious inhalatory exposures and variants in genes in the causation of COPD. Genes will be selected using two strategies: First, genes predisposed to an interaction due their involvement in inflammatory or protective mechanisms will be chosen. Second, the whole DNA will be investigated using modern laboratory methods, with the possibility to discover new important variants.

Relevance

The project could make an important contribution to understanding the biological mechanisms causing COPD. The findings might help explain why some persons develop COPD without being substantially exposed to tobacco or pollution, while others don't get the disease although they actively smoke.
This knowledge might lead to the development of easy to apply and cost-effective preventive measures such as dietary changes or intake of vitamin supplements that are anti-oxidative. Given the still limited option to treat COPD, preventive measures are of major importance.
Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants

Employees

Publications

Publication
Different genes interact with particulate matter and tobacco smoke exposure in affecting lung function decline in the general population.
Curjuric Ivan (2012), Different genes interact with particulate matter and tobacco smoke exposure in affecting lung function decline in the general population., in PLoS One, 7(7), e40175.
Determinants of change in airway reactivity over 11 years in the SAPALDIA population study.
Curjuric I, Zemp E, Dratva J, Ackermann-Liebrich U, Bridevaux P-O, Bettschart R W, Brutsche M, Frey M, Gerbase M W, Knöpfli B, Künzli N, Pons M, Schwartz J, Schindler C, Rochat T, SAPALDIA team (2011), Determinants of change in airway reactivity over 11 years in the SAPALDIA population study., in The European respiratory journal : official journal of the European Society for Clinical Respiratory, 37(3), 492-500.
HMOX1 and GST variants modify attenuation of FEF25-75% decline due to PM10 reduction.
Curjuric I, Imboden M, Schindler C, Downs S H, Hersberger M, Liu S L J, Matyas G, Russi E W, Schwartz J, Thun G A, Postma D S, Rochat T, Probst-Hensch N M, SAPALDIA team (2010), HMOX1 and GST variants modify attenuation of FEF25-75% decline due to PM10 reduction., in The European respiratory journal : official journal of the European Society for Clinical Respiratory, 35(3), 505-14.
Longitudinal change of prebronchodilator spirometric obstruction and health outcomes: results from the SAPALDIA cohort.
Probst-Hensch N M, Curjuric I, Pierre-Olivier B, Ackermann-Liebrich U, Bettschart R W, Brändli O, Brutsche M, Burdet L, Gerbase M W, Knöpfli B, Künzli N, Pons M G, Schindler C, Tschopp J-M, Rochat T, Russi E W (2010), Longitudinal change of prebronchodilator spirometric obstruction and health outcomes: results from the SAPALDIA cohort., in Thorax, 65(2), 150-6.
Perimenstrual increase in bronchial hyperreactivity in premenopausal women: results from the population-based SAPALDIA 2 cohort.
Dratva Julia, Schindler Christian, Curjuric Ivan, Stolz Daiana, Macsali Ferenc, Gomez Francisco Real, Zemp Elisabeth, SAPALDIA Team (2010), Perimenstrual increase in bronchial hyperreactivity in premenopausal women: results from the population-based SAPALDIA 2 cohort., in The Journal of allergy and clinical immunology, 125(4), 823-9.
Prevalence of airflow obstruction in smokers and never-smokers in Switzerland.
Bridevaux P-O, Probst-Hensch N M, Schindler C, Curjuric I, Felber Dietrich D, Braendli O, Brutsche M, Burdet L, Frey M, Gerbase M W, Ackermann-Liebrich U, Pons M, Tschopp J-M, Rochat T, Russi E W (2010), Prevalence of airflow obstruction in smokers and never-smokers in Switzerland., in The European respiratory journal : official journal of the European Society for Clinical Respiratory, 36(6), 1259-69.
Decreased PM10 exposure attenuates age-related lung function decline: genetic variants in p53, p21, and CCND1 modify this effect.
Imboden Medea, Schwartz Joel, Schindler Christian, Curjuric Ivan, Berger Wolfgang, Liu Sally L J, Russi Erich W, Ackermann-Liebrich Ursula, Rochat Thierry, Probst-Hensch Nicole M, SAPALDIA Team (2009), Decreased PM10 exposure attenuates age-related lung function decline: genetic variants in p53, p21, and CCND1 modify this effect., in Environmental health perspectives, 117(9), 1420-7.
Sex-specific effect of body weight gain on systemic inflammation in subjects with COPD: results from the SAPALDIA cohort study 2.
Bridevaux P-O, Gerbase M W, Schindler C, Dietrich D Felber, Curjuric I, Dratva J, Ackermann-Liebrich U, Probst-Hensch N M, Gaspoz J-M, Rochat T (2009), Sex-specific effect of body weight gain on systemic inflammation in subjects with COPD: results from the SAPALDIA cohort study 2., in The European respiratory journal : official journal of the European Society for Clinical Respiratory, 34(2), 332-9.
A genome-wide meta-analysis of genetic variants associated with allergic rhinitis and grass sensitization and their interaction with birth order.
Ramasamy Adaikalavan, Curjuric Ivan, Coin Lachlan J, Kumar Ashish, McArdle Wendy L, Imboden Medea, Leynaert Benedicte, Kogevinas Manolis, Schmid-Grendelmeier Peter, Pekkanen Juha, Wjst Matthias, Bircher Andreas J, Sovio Ulla, Rochat Thierry, Hartikainen Anna-Liisa, Balding David J, Jarvelin Marjo-Riitta, Probst-Hensch Nicole, Strachan David P, Jarvis Deborah L, A genome-wide meta-analysis of genetic variants associated with allergic rhinitis and grass sensitization and their interaction with birth order., in The Journal of allergy and clinical immunology, 128(5), 996-1005.
Authors' response.
Probst-Hensch Nicole M, Curjuric Ivan, Bridevaux Pierre-Olivier, Künzli Nino, Schindler Christian, Rochat Thierry, Authors' response., in Thorax.
Genome-wide association and large-scale follow up identifies 16 new loci influencing lung function.
Artigas María Soler, Loth Daan W, Wain Louise V, Gharib Sina A, Obeidat Ma'en, Tang Wenbo, Zhai Guangju, Zhao Jing Hua, Smith Albert Vernon, Huffman Jennifer E, Albrecht Eva, Jackson Catherine M, Evans David M, Cadby Gemma, Fornage Myriam, Manichaikul Ani, Lopez Lorna M, Johnson Toby, Aldrich Melinda C, Aspelund Thor, Barroso Inês, Campbell Harry, Cassano Patricia A, Couper David J, Eiriksdottir Gudny, Genome-wide association and large-scale follow up identifies 16 new loci influencing lung function., in Nature genetics, 43(11), 1082-1090.

Scientific events

Associated projects

Number Title Start Funding scheme
134276 Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults (SAPALDIA) 01.04.2011 Cohort Studies Large
148470 SAPALDIA Cohort on Healthy Aging 01.04.2014 Cohort Studies Large
177506 SAPALDIA 5 - Cohort on Healthy Aging 01.04.2018 Cohort Studies Large

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