title: The role of IREB2 and transforming growth factor beta-1 genetic variants in COPD: a replication case-control study.
abstract: BACKGROUND
  Genetic factors are known to contribute to COPD susceptibility and these factors are not fully understood. Conflicting results have been reported for many genetic studies of candidate genes based on their role in the disease. Genome-wide association studies in combination with expression profiling have identified a number of new candidates including IREB2. A meta-analysis has implicated transforming growth factor beta-1 (TGFbeta1) as a contributor to disease susceptibility.
  
  
  METHODS
  We have examined previously reported associations in both genes in a collection of 1017 white COPD patients and 912 non-diseased smoking controls. Genotype information was obtained for seven SNPs in the IREB2 gene, and for four SNPs in the TGFbeta1 gene. Allele and genotype frequencies were compared between COPD cases and controls, and odds ratios were calculated. The analysis was adjusted for age, sex, smoking and centre, including interactions of age, sex and smoking with centre.
  
  
  RESULTS
  Our data replicate the association of IREB2 SNPs in association with COPD for SNP rs2568494, rs2656069 and rs12593229 with respective adjusted p-values of 0.0018, 0.0039 and 0.0053. No significant associations were identified for TGFbeta1.
  
  
  CONCLUSIONS
  These studies have therefore confirmed that the IREB2 locus is a contributor to COPD susceptibility and suggests a new pathway in COPD pathogenesis invoking iron homeostasis.
authors.affiliation: The University of Nottingham, School of Molecular Medical Sciences, University Hospital, Queens Medical Centre, Nottingham, UK.
authors.forename: Sally L
authors.initials: SL
authors.lastname: Chappell
authors.forename: Leslie
authors.initials: L
authors.lastname: Daly
authors.forename: Juzer
authors.initials: J
authors.lastname: Lotya
authors.forename: Aiman
authors.initials: A
authors.lastname: Alsaegh
authors.forename: Tamar
authors.initials: T
authors.lastname: Guetta-Baranes
authors.forename: Josep
authors.initials: J
authors.lastname: Roca
authors.forename: Roberto
authors.initials: R
authors.lastname: Rabinovich
authors.forename: Kevin
authors.initials: K
authors.lastname: Morgan
authors.forename: Ann B
authors.initials: AB
authors.lastname: Millar
authors.forename: Seamas C
authors.initials: SC
authors.lastname: Donnelly
authors.forename: Vera
authors.initials: V
authors.lastname: Keatings
authors.forename: William
authors.initials: W
authors.lastname: MacNee
authors.forename: Jan
authors.initials: J
authors.lastname: Stolk
authors.forename: Pieter S
authors.initials: PS
authors.lastname: Hiemstra
authors.forename: Massimo
authors.initials: M
authors.lastname: Miniati
authors.forename: Simonetta
authors.initials: S
authors.lastname: Monti
authors.forename: Clare M
authors.initials: CM
authors.lastname: O'Connor
authors.forename: Noor
authors.initials: N
authors.lastname: Kalsheker
mesh_terms: D000368:Aged; D000483:Alleles; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D006801:Humans; D007501:Iron / Q000378:metabolism; D035942:Iron Regulatory Protein 2 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D029424:Pulmonary Disease, Chronic Obstructive / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000235:genetics*
chemical_list: D053773:Transforming Growth Factor beta1; D007501:Iron; D035942:Iron Regulatory Protein 2