title: Polymorphism of genes related to cardiovascular disease in patients with rheumatoid arthritis.
abstract: OBJECTIVE
  To analyze candidate genes, related to cardiovascular disease (CVD) in general, and potentially involved in the inflammatory process, in RA patients from northern Sweden.
  
  
  METHODS
  Four hundred and sixty-seven individuals (345 females; 122 males) with RA (ACR criteria), having a mean age of 61.8 +/- 13.0 years and mean disease duration of 16.2 +/- 12.1 years, were consecutively recruited and followed-up for 3 years. The prevalence of CVD, [(ischemic heart disease (IHD), deep vein thromboses/pulmonary embolism (DVT/PE) and/or stroke/TIA] and hypertension was registered. Candidate genes encoding for Beta-fibrinogen (G-455A), Factor XIIIA (Val34Leu), plasminogen activator inhibitor type-1 (PAI-1 4G/5G), and tumor necrosis factor receptor (TNFR)II (M196R) were analysed. Controls (n = 672) were randomly selected according to age and gender from the Medical Biobank of Northern Sweden. Polymorphisms were genotyped using a TaqMan 9700HT and the 5'nuclease allelic discrimination assay.
  
  
  RESULTS
  The genotypes, carriers and alleles did not differ in distribution between patients and controls. Carriage of the TNFRII R variant was more frequent among patients with hypertension (p = 0.018). The genotype distribution of PAI-1 in patients with IHD differed significantly (p = 0.002) because carriage of 4G was more frequent (p = 0.024). Combined carriage of TNFRII 196R variant and Beta-fibrinogen-455A was a stronger predictor for hypertension than each genotype separately. The distribution of FXIIIA genotypes deviated significantly in RA patients with DVT/PE (p = 0.028) with an increased frequency of the Leu34 variant.
  
  
  CONCLUSIONS
  The unusual alleles of TNFRII, PAI-1 and FXIIIA were associated with CVD in RA patients. The combination of several of the rare types further increased the predictive values for CVD.
authors.affiliation: Department of Public Health and Clinical Medicine/Rheumatology and Medicine, University Hospital, Umeå, Sweden.
authors.forename: L
authors.initials: L
authors.lastname: Arlestig
authors.forename: S
authors.initials: S
authors.lastname: Wållberg Jonsson
authors.forename: B
authors.initials: B
authors.lastname: Stegmayr
authors.forename: S
authors.initials: S
authors.lastname: Rantapää-Dahlqvist
mesh_terms: D000483:Alleles; D001172:Arthritis, Rheumatoid / Q000150:complications*; D002318:Cardiovascular Diseases / Q000235:genetics*; D026122:Factor XIIIa / Q000235:genetics; D005260:Female; D005340:Fibrinogen / Q000235:genetics; D005500:Follow-Up Studies; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D006973:Hypertension / Q000235:genetics; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000235:genetics; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics; D011110:Polymorphism, Genetic; D011655:Pulmonary Embolism / Q000235:genetics; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics; D020521:Stroke / Q000235:genetics; D020246:Venous Thrombosis / Q000235:genetics
chemical_list: D017395:Plasminogen Activator Inhibitor 1; D018124:Receptors, Tumor Necrosis Factor; D005340:Fibrinogen; D026122:Factor XIIIa