title: Interaction between smoking and functional polymorphism in the TGFB1 gene is associated with ischaemic heart disease and myocardial infarction in patients with rheumatoid arthritis: a cross-sectional study.
abstract: BACKGROUND
  Transforming growth factor-beta1 (TGF-beta1) is a pleiotropic cytokine that plays important roles in immunity and inflammation. Some studies have suggested that polymorphism in the TGFB1 gene is associated with heart disease in the general population. The purpose of the present study was to determine whether common single-nucleotide polymorphisms (SNP) in the TGFB1 gene are associated with ischaemic heart disease (IHD) and/or myocardial infarction (MI) in patients with rheumatoid arthritis (RA), and to investigate the influence of smoking on any association.
  
  
  METHODS
  PCR-based assays were used to determine the genotypes of TGFB1 SNPs including TGFB1-509 C/T (rs1800469, in the promoter region), +868 T/C (rs1800470, in exon 1) and +913 G/C (rs1800471, in exon 1) in 414 subjects with established RA. Genotyping for the +868 SNP was also carried out on a second study population of RA patients (n = 259) with early disease. Serum levels of TGF-beta1 were measured using a commercial ELISA kit. Smoking history and IHD/MI status were obtained on each patient. Associations with IHD/MI were assessed using contingency tables and logistic regression analyses.
  
  
  RESULTS
  The heterozygous genotype of TGFB+868 was associated with an increased risk of IHD (OR 2.14, 95% CI 1.30 - 3.55) and MI (OR 2.42, 95% CI 1.30-4.50), compared to the homozygous genotypes combined. Smoking was an independent risk for IHD and MI, and evidence of interaction between smoking and TGFB+868 was found. Multivariate analyses indicated that the strongest associations with IHD and MI were due to the combined effect of the TGFB1+868 TC genotype and smoking (OR 2.75, 95% CI 1.59-4.75; and OR 2.58 95% CI 1.33-4.99, respectively), independent of other cardiovascular risk factors. The association of the +868 TC genotype and evidence of +868 TC-smoking interaction with IHD were replicated in a second population of RA patients with early disease. Serum TGF-beta1 levels were not associated with TGFB1 genetic variations, smoking or IHD/MI status.
  
  
  CONCLUSIONS
  Interaction between smoking and polymorphism in the TGFB1 gene may influence the risk of IHD and MI in patients with RA.
authors.affiliation: Haywood Rheumatology Centre, Haywood Hospital, High Lane, Burslem, Stoke-on-Trent, Staffordshire, ST6 7AG, UK.
authors.forename: Ying
authors.initials: Y
authors.lastname: Chen
authors.forename: Peter T
authors.initials: PT
authors.lastname: Dawes
authors.forename: Jon C
authors.initials: JC
authors.lastname: Packham
authors.forename: Derek L
authors.initials: DL
authors.lastname: Mattey
mesh_terms: D000368:Aged; D001172:Arthritis, Rheumatoid / Q000453:epidemiology / Q000235:genetics*; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D005260:Female; D056726:Genetic Association Studies / Q000379:methods; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000453:epidemiology / Q000235:genetics*; D017202:Myocardial Ischemia / Q000453:epidemiology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012907:Smoking / Q000235:genetics*; D053773:Transforming Growth Factor beta1 / Q000235:genetics*
chemical_list: C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1