title: Effect of gene environment interactions on lung function and cardiovascular disease in COPD.
abstract: BACKGROUND
  The objective of this study was to determine if gene-environment interactions between cigarette smoking and interleukin-6 (IL6), interferon-γ (IFNG), interleukin-1β (IL1B), or interleukin-1 receptor antagonist (IL1RN) single nucleotide polymorphisms are associated with lung function decline and cardiovascular disease in chronic obstructive pulmonary disease (COPD).
  
  
  METHODS
  Single nucleotide polymorphisms (SNPs) in IL6, IFNG, IL1B, and IL1RN were genotyped in the Lung Health Study and correlated with rate of decline of forced expiratory volume in 1 second (FEV(1)) over 5 years, baseline FEV(1), serum protein levels, cardiovascular disease, and interactions with smoking.
  
  
  RESULTS
  The IL6 rs2069825 single nucleotide polymorphism was associated with the rate of decline of prebronchodilator FEV(1) (P = 0.049), and was found to have a significant interaction (P = 0.004) with mean number of cigarettes smoked per day. There was also a significant interaction of IFNG rs2069727 with smoking on prebronchodilator (P = 0.008) and postbronchodilator (P =0.01) FEV(1.) The IL6 polymorphism was also associated with cardiovascular disease in heterozygous individuals (P = 0.044), and was found to have a significant interaction with smoking (P = 0.024). None of the genetic variants were associated with their respective serum protein levels.
  
  
  CONCLUSIONS
  The results suggest interactions of IL6 rs2069825 and IFNG rs2069727 single nucleotide polymorphisms with cigarette smoking on measures of lung function. The IL6 rs2069825 single nucleotide polymorphism also interacted with smoking to affect the risk of cardiovascular disease in COPD patients.
authors.affiliation: University of British Columbia, James Hogg Research Laboratories, St Paul's Hospital, Division of Respirology, Department of Medicine, Vancouver, BC, Canada.
authors.forename: Tillie-Louise
authors.initials: TL
authors.lastname: Hackett
authors.forename: Dorota
authors.initials: D
authors.lastname: Stefanowicz
authors.forename: Farzian
authors.initials: F
authors.lastname: Aminuddin
authors.forename: Don D
authors.initials: DD
authors.lastname: Sin
authors.forename: John E
authors.initials: JE
authors.lastname: Connett
authors.forename: Nicholas R
authors.initials: NR
authors.lastname: Anthonisen
authors.forename: Peter D
authors.initials: PD
authors.lastname: Paré
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Sandford
mesh_terms: D000328:Adult; D002170:Canada; D002318:Cardiovascular Diseases / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D005541:Forced Expiratory Volume; D005787:Gene Frequency; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease; D006801:Humans; D007371:Interferon-gamma / Q000097:blood / Q000235:genetics; D053590:Interleukin 1 Receptor Antagonist Protein / Q000097:blood / Q000235:genetics; D053583:Interleukin-1beta / Q000097:blood / Q000235:genetics; D015850:Interleukin-6 / Q000097:blood / Q000235:genetics; D016014:Linear Models; D015810:Linkage Disequilibrium; D016015:Logistic Models; D008168:Lung / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D029424:Pulmonary Disease, Chronic Obstructive / Q000097:blood / Q000150:complications / Q000235:genetics* / Q000503:physiopathology; D018570:Risk Assessment; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects*; D013997:Time Factors
chemical_list: C507763:IL1RN protein, human; C508600:IL6 protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D053583:Interleukin-1beta; D015850:Interleukin-6; D007371:Interferon-gamma