Different Genes Interact with Particulate Matter and Tobacco Smoke Exposure in Affecting Lung Function Decline in the General Population

Background Oxidative stress related genes modify the effects of ambient air pollution or tobacco smoking on lung function decline. The impact of interactions might be substantial, but previous studies mostly focused on main effects of single genes. Objectives We studied the interaction of both exposures with a broad set of oxidative-stress related candidate genes and pathways on lung function decline and contrasted interactions between exposures. Methods For 12679 single nucleotide polymorphisms (SNPs), change in forced expiratory volume in one second (FEV1), FEV1 over forced vital capacity (FEV1/FVC), and mean forced expiratory flow between 25 and 75% of the FVC (FEF25-75) was regressed on interval exposure to particulate matter <10 µm in diameter (PM10) or packyears smoked (a), additive SNP effects (b), and interaction terms between (a) and (b) in 669 adults with GWAS data. Interaction p-values for 152 genes and 14 pathways were calculated by the adaptive rank truncation product (ARTP) method, and compared between exposures. Interaction effect sizes were contrasted for the strongest SNPs of nominally significant genes (pinteraction<0.05). Replication was attempted for SNPs with MAF>10% in 3320 SAPALDIA participants without GWAS. Results On the SNP-level, rs2035268 in gene SNCA accelerated FEV1/FVC decline by 3.8% (pinteraction = 2.5×10−6), and rs12190800 in PARK2 attenuated FEV1 decline by 95.1 ml pinteraction = 9.7×10−8) over 11 years, while interacting with PM10. Genes and pathways nominally interacting with PM10 and packyears exposure differed substantially. Gene CRISP2 presented a significant interaction with PM10 (pinteraction = 3.0×10−4) on FEV1/FVC decline. Pathway interactions were weak. Replications for the strongest SNPs in PARK2 and CRISP2 were not successful. Conclusions Consistent with a stratified response to increasing oxidative stress, different genes and pathways potentially mediate PM10 and tobacco smoke effects on lung function decline. Ignoring environmental exposures would miss these patterns, but achieving sufficient sample size and comparability across study samples is challenging.

[1]  A. Brody,et al.  Analysis of airspace and interstitial mononuclear cell populations in human diffuse interstitial lung disease. , 2015, The American review of respiratory disease.

[2]  Lorna M. Lopez,et al.  Genome-wide association and large scale follow-up identifies 16 new loci influencing lung function , 2011, Nature Genetics.

[3]  David M. Evans,et al.  A Comprehensive Evaluation of Potential Lung Function Associated Genes in the SpiroMeta General Population Sample , 2011, PloS one.

[4]  B. Fridley,et al.  Gene set analysis of SNP data: benefits, challenges, and future directions , 2011, European Journal of Human Genetics.

[5]  L. Edwards,et al.  Loci identified by genome-wide association studies influence different disease-related phenotypes in chronic obstructive pulmonary disease. , 2010, American journal of respiratory and critical care medicine.

[6]  G. Abecasis,et al.  MaCH: using sequence and genotype data to estimate haplotypes and unobserved genotypes , 2010, Genetic epidemiology.

[7]  A. Urbani,et al.  Markers of anti-oxidant response in tobacco smoke exposed subjects: a data-mining review. , 2010, Pulmonary pharmacology & therapeutics.

[8]  P. Burney,et al.  Forced vital capacity, airway obstruction and survival in a general population sample from the USA , 2010, Thorax.

[9]  James S. Brown,et al.  Particulate Matter–Induced Health Effects: Who Is Susceptible? , 2010, Environmental health perspectives.

[10]  Florence Demenais,et al.  A large-scale, consortium-based genomewide association study of asthma. , 2010, The New England journal of medicine.

[11]  I. Hall,et al.  The genetics of obstructive lung disease: big is beautiful , 2010, Thorax.

[12]  J. Kongerud,et al.  Dust exposure assessed by a job exposure matrix is associated with increased annual decline in FEV1: a 5-year prospective study of employees in Norwegian smelters. , 2010, American journal of respiratory and critical care medicine.

[13]  C. Hersh.  Faculty Opinions recommendation of Genome-wide association study identifies five loci associated with lung function. , 2010 .

[14]  D. Thomas,et al.  Methods for investigating gene-environment interactions in candidate pathway and genome-wide association studies. , 2010, Annual review of public health.

[15]  Yurii S. Aulchenko,et al.  ProbABEL package for genome-wide association analysis of imputed data , 2010, BMC Bioinformatics.

[16]  D. Postma,et al.  HMOX1 and GST variants modify attenuation of FEF25-75% decline due to PM10 reduction. , 2010, The European respiratory journal.

[17]  Christoph Lange,et al.  Variants in FAM13A are associated with chronic obstructive pulmonary disease , 2010, Nature Genetics.

[18]  A. Hofman,et al.  Hedgehog-interacting protein is a COPD susceptibility gene: the Rotterdam Study , 2009, European Respiratory Journal.

[19]  P. Rosenberg,et al.  Pathway analysis by adaptive combination of P‐values , 2009, Genetic epidemiology.

[20]  D. Postma,et al.  Meta-analyses on suspected chronic obstructive pulmonary disease genes: a summary of 20 years' research. , 2009, American journal of respiratory and critical care medicine.

[21]  A. Nel,et al.  Particulate matter and atherosclerosis: role of particle size, composition and oxidative stress , 2009, Particle and Fibre Toxicology.

[22]  E. Silverman,et al.  Genetics and genomics of chronic obstructive pulmonary disease. , 2009, Proceedings of the American Thoracic Society.

[23]  M. Gaca,et al.  The role of oxidative stress in the biological responses of lung epithelial cells to cigarette smoke , 2009, Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals.

[24]  K. Shianna,et al.  A Genome-Wide Association Study in Chronic Obstructive Pulmonary Disease (COPD): Identification of Two Major Susceptibility Loci , 2009, PLoS genetics.

[25]  Scott T. Weiss,et al.  A Genome-Wide Association Study of Pulmonary Function Measures in the Framingham Heart Study , 2009, PLoS genetics.

[26]  J. Bousquet,et al.  Effect of 17q21 variants and smoking exposure in early-onset asthma. , 2008, The New England journal of medicine.

[27]  S. Ryter,et al.  RETRACTED ARTICLE: Autophagic proteins regulate cigarette smoke induced apoptosis: Protective role of heme oxygenase-1 , 2008, Autophagy.

[28]  Peter Kraft,et al.  Curses--winner's and otherwise--in genetic epidemiology. , 2008, Epidemiology.

[29]  Cleo C. van Diemen,et al.  Lung function loss, smoking, vitamin C intake, and polymorphisms of the glutamate-cysteine ligase genes. , 2008, American journal of respiratory and critical care medicine.

[30]  S T Holgate,et al.  Genetic susceptibility to the respiratory effects of air pollution , 2008, Thorax.

[31]  L. Le Marchand,et al.  Design Considerations for Genomic Association Studies: Importance of Gene-Environment Interactions , 2008, Cancer Epidemiology Biomarkers & Prevention.

[32]  N. Probst-Hensch,et al.  Reduced exposure to PM10 and attenuated age-related decline in lung function. , 2007, The New England journal of medicine.

[33]  U. Ackermann-Liebrich,et al.  Characterization of Source-Specific Air Pollution Exposure for a Large Population-Based Swiss Cohort (SAPALDIA) , 2007, Environmental health perspectives.

[34]  S Katharine Hammond,et al.  Secondhand smoke exposure, pulmonary function, and cardiovascular mortality. , 2007, Annals of epidemiology.

[35]  I. Adcock,et al.  Oxidative stress and redox regulation of lung inflammation in COPD , 2006, European Respiratory Journal.

[36]  M. Tanito,et al.  Thioredoxin-1 suppresses lung injury and apoptosis induced by diesel exhaust particles (DEP) by scavenging reactive oxygen species and by inhibiting DEP-induced downregulation of Akt. , 2005, Free radical biology & medicine.

[37]  C. Nickel,et al.  Plasmodium falciparum 2-Cys peroxiredoxin reacts with plasmoredoxin and peroxynitrite , 2005, Biological chemistry.

[38]  M. Kogevinas,et al.  Lung function decline, chronic bronchitis, and occupational exposures in young adults. , 2005, American journal of respiratory and critical care medicine.

[39]  U. Ackermann-Liebrich,et al.  Longitudinal validity of spirometers--a challenge in longitudinal studies. , 2005, Swiss medical weekly.

[40]  M. Imboden,et al.  Follow-up of the Swiss Cohort Study on Air Pollution and Lung Diseases in Adults (SAPALDIA 2) 1991–2003: methods and characterization of participants , 2005, Sozial- und Präventivmedizin/Social and Preventive Medicine.

[41]  J. Erikssen,et al.  Lung function, smoking and mortality in a 26-year follow-up of healthy middle-aged males , 2005, European Respiratory Journal.

[42]  P. Paré,et al.  Glutathione S-transferase variants and their interaction with smoking on lung function. , 2004, American journal of respiratory and critical care medicine.

[43]  D. Postma,et al.  Acute effects of cigarette smoke on inflammation and oxidative stress: a review , 2004, Thorax.

[44]  M. Volkert,et al.  Stress Induction and Mitochondrial Localization of Oxr1 Proteins in Yeast and Humans , 2004, Molecular and Cellular Biology.

[45]  S. Mao,et al.  Purification of human haptoglobin 1-1, 2-1, and 2-2 using monoclonal antibody affinity chromatography. , 2004, Protein expression and purification.

[46]  Andre E Nel,et al.  Particulate air pollutants and asthma. A paradigm for the role of oxidative stress in PM-induced adverse health effects. , 2003, Clinical immunology.

[47]  M. Olivier.  A haplotype map of the human genome. , 2003, Nature.

[48]  M. Olivier.  A haplotype map of the human genome , 2003, Nature.

[49]  Ning Li,et al.  USE OF A STRATIFIED OXIDATIVE STRESS MODEL TO STUDY THE BIOLOGICAL EFFECTS OF AMBIENT CONCENTRATED AND DIESEL EXHAUST PARTICULATE MATTER , 2002, Inhalation toxicology.

[50]  J. Tamaoki,et al.  Acute cigarette smoke exposure induces apoptosis of alveolar macrophages. , 2001, American journal of physiology. Lung cellular and molecular physiology.

[51]  W Winkelstein,et al.  Pulmonary function is a long-term predictor of mortality in the general population: 29-year follow-up of the Buffalo Health Study. , 2000, Chest.

[52]  M. Ashburner,et al.  Gene Ontology: tool for the unification of biology , 2000, Nature Genetics.

[53]  G. Avataneo,et al.  Dust exposure, respiratory symptoms, and longitudinal decline of lung function in young coal miners. , 1996, Occupational and environmental medicine.

[54]  John L. Hankinson,et al.  Standardization of Spirometry, 1994 Update. American Thoracic Society. , 1995, American journal of respiratory and critical care medicine.

[55]  U Ackermann-Liebrich,et al.  Variability of FVC and FEV1 due to technician, team, device and subject in an eight centre study: three quality control studies in SAPALDIA. Swiss Study on Air Pollution and Lung Disease in Adults. , 1995, The European respiratory journal.

[56]  Buist As.  Standardization of spirometry. , 1987 .

[57]  J. Lellouch,et al.  Occupational exposure and 12-year spirometric changes among Paris area workers. , 1982, British journal of industrial medicine.

[58]  D. Strachan,et al.  Gene-environment interaction for childhood asthma and exposure to farming in Central Europe. , 2011, The Journal of allergy and clinical immunology.

[59]  A. Hofman,et al.  Meta-analyses of genome-wide association studies identify multiple loci associated with pulmonary function , 2010, Nature Genetics.

[60]  Simon C Watkins,et al.  Cigarette smoke-induced mitochondrial dysfunction and oxidative stress in Toorn , 2009 .

[61]  T. Otsuki,et al.  Gene expression in rat lungs during early response to paraquat-induced oxidative stress. , 2006, International journal of molecular medicine.

[62]  Wj Gauderman,et al.  QUANTO 1.1: A computer program for power and sample size calculations for genetic-epidemiology studies , 2006 .

[63]  W. MacNee,et al.  Pulmonary and systemic oxidant/antioxidant imbalance in chronic obstructive pulmonary disease. , 2005, Proceedings of the American Thoracic Society.

[64]  U. Ackermann-Liebrich,et al.  SAPALDIA: Methods and participation in the cross-sectional part of the Swiss Study on Air Pollution and Lung Diseases in Adults , 2005, Sozial- und Präventivmedizin.

[65]  Terrence S. Furey,et al.  The UCSC Table Browser data retrieval tool , 2004, Nucleic Acids Res..

[66]  R. Klocke,et al.  THE AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE , 1994 .

[67]  P. Schnohr,et al.  Spirometric findings and mortality in never-smokers. , 1990, Journal of clinical epidemiology.

[68]  A. Buist.  Standardization of spirometry. , 1987, The American review of respiratory disease.