title: Polymorphisms of the genes encoding CD40 and growth differentiation factor 15 and in the 9p21.3 region in patients with rheumatoid arthritis and cardiovascular disease.
abstract: OBJECTIVE
  Genes or gene products associated with coronary artery disease in the general population were analyzed in rheumatoid arthritis (RA) patients with atherothrombotic manifestations (ATM).
  
  
  METHODS
  A cross-sectional study of 681 individuals (498 women; 183 men) with RA (American College of Rheumatology criteria), a mean age of 60.6 ± 13.2 years, and mean disease duration of 15.5 ± 12.6 years who were consecutively recruited and followed for 6 years. The prevalence of ATM [i.e., myocardial infarction, angina pectoris with intervention, deep vein thrombosis/pulmonary embolism (DVT/PE), and/or stroke/transient ischemic attack (TIA)] was recorded. Polymorphisms were analyzed in the genes coding for growth differentiation factor 15 (GDF15)/monocyte inhibitory cytokine-1 (MIC-1; rs1058587), CD40 (rs1535045 and rs3765459), and the 9p21.3 locus (rs1333049). Controls were randomly selected (n = 687; matched for age and sex).
  
  
  RESULTS
  The distribution of genotypes of GDF15/MIC-1 differed significantly between patients with RA and controls (chi-squared = 6.40, 2 df, p = 0.041). ATM were associated with polymorphism of the GDF15/MIC-1 G allele (OR 2.21, 95% CI 1.17-4.18), and with CC genotype of the 9p21.3 locus (rs1333049; OR 1.92, 95% CI 1.15-3.19). Stroke/TIA in women was associated with GDF15/MIC-1 GG genotype (OR 3.75, 95% CI 1.06-13.33), while stroke/TIA in men was associated with CD40 homozygous major alleles (OR 6.48, 95% CI 1.31-32.0 and OR 2.78, 95% CI 0.78-9.91, respectively). DVT/PE was associated with polymorphism in the GDF15/MIC-1 gene (rs1058587) minor allele (OR 3.53, 95% CI 1.30-9.58).
  
  
  CONCLUSIONS
  The gene polymorphisms analyzed were associated with different ATM in RA. The GDF15/MIC-1 gene polymorphism was also associated with RA per se, suggesting a common etiology for RA and ATM.
authors.affiliation: Department of Public Health and Clinical Medicine, Rheumatology, Umeå University, Umeå, Sweden.
authors.forename: Lisbeth
authors.initials: L
authors.lastname: Ärlestig
authors.forename: Solbritt
authors.initials: S
authors.lastname: Rantapää-Dahlqvist
mesh_terms: D000368:Aged; D001161:Arteriosclerosis / Q000453:epidemiology / Q000235:genetics; D001172:Arthritis, Rheumatoid / Q000453:epidemiology / Q000235:genetics*; D019013:CD40 Antigens / Q000235:genetics*; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000235:genetics*; D003430:Cross-Sectional Studies; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics; D005838:Genotype; D055436:Growth Differentiation Factor 15 / Q000235:genetics*; D006801:Humans; D006973:Hypertension / Q000453:epidemiology / Q000235:genetics; D002546:Ischemic Attack, Transient / Q000453:epidemiology / Q000235:genetics; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D015995:Prevalence; D011655:Pulmonary Embolism / Q000453:epidemiology / Q000235:genetics; D012307:Risk Factors; D020521:Stroke / Q000453:epidemiology / Q000235:genetics; D020246:Venous Thrombosis / Q000453:epidemiology / Q000235:genetics
chemical_list: D019013:CD40 Antigens; C526140:GDF15 protein, human; D055436:Growth Differentiation Factor 15