Genes and pathways underlying susceptibility to impaired lung function in the context of environmental tobacco smoke exposure

Respiratory Research

Research

A. Hofman¹  L. Lahousse²  G.G. Brusselle³  J.M. Vonk⁴  K. de Jong⁴  H.M. Boezen⁴  D.S. Postma⁵  N.M. Probst-Hensch⁶  M. Imboden⁶ 

[1] Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands;Department of Internal Medicine, Erasmus Medical Center, Rotterdam, the Netherlands;Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands;Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium;Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands;Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium;Department of Respiratory Medicine, Erasmus Medical Center, Rotterdam, the Netherlands;Department of Epidemiology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9700 RB, Groningen, the Netherlands;Groningen Research Institute for Asthma and COPD (GRIAC), University of Groningen, University Medical Center Groningen, Groningen, the Netherlands;Department of Pulmonary Diseases, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands;Groningen Research Institute for Asthma and COPD (GRIAC), University of Groningen, University Medical Center Groningen, Groningen, the Netherlands;Swiss Tropical and Public Health Institute, Basel, Switzerland;University of Basel, Basel, Switzerland;

关键词: Environmental tobacco smoke pollution;    Single nucleotide polymorphism;    Forced expiratory volume;   

DOI  :  10.1186/s12931-017-0625-7

 received in 2017-02-13, accepted in 2017-07-18,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundStudies aiming to assess genetic susceptibility for impaired lung function levels upon exposure to environmental tobacco smoke (ETS) have thus far focused on candidate-genes selected based on a-priori knowledge of potentially relevant biological pathways, such as glutathione S-transferases and ADAM33. By using a hypothesis-free approach, we aimed to identify novel susceptibility loci, and additionally explored biological pathways potentially underlying this susceptibility to impaired lung function in the context of ETS exposure.MethodsGenome-wide interactions of single nucleotide polymorphism (SNP) by ETS exposure (0 versus ≥1 h/day) in relation to the level of forced expiratory volume in one second (FEV1) were investigated in 10,817 subjects from the Dutch LifeLines cohort study, and verified in subjects from the Swiss SAPALDIA study (n = 1276) and the Dutch Rotterdam Study (n = 1156). SNP-by-ETS exposure p-values obtained from the identification analysis were used to perform a pathway analysis.ResultsFourty Five SNP-by-ETS exposure interactions with p-values <10−4 were identified in the LifeLines study, two being replicated with nominally significant p-values (<0.05) in at least one of the replication cohorts. Three pathways were enriched in the pathway-level analysis performed in the identification cohort LifeLines, i.E. the apoptosis, p38 MAPK and TNF pathways.ConclusionThis unique, first genome-wide gene-by-ETS interaction study on the level of FEV1 showed that pathways previously implicated in chronic obstructive pulmonary disease (COPD), a disease characterized by airflow obstruction, may also underlie susceptibility to impaired lung function in the context of ETS exposure.

【 授权许可】

CC BY   
© The Author(s). 2017