Polymorphism of genes related to cardiovascular disease in patients with rheumatoid arthritis.
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.
Arlestig
L
L
Department of Public Health and Clinical Medicine/Rheumatology and Medicine, University Hospital, Umeå, Sweden.
Wållberg Jonsson
S
S
Stegmayr
B
B
Rantapää-Dahlqvist
S
S
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
D017395:Plasminogen Activator Inhibitor 1; D018124:Receptors, Tumor Necrosis Factor; D005340:Fibrinogen; D026122:Factor XIIIa