Rheumatology Advance Access published online on December 23, 2008
Rheumatology, doi:10.1093/rheumatology/ken443
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Transforming growth factor-β1 869T/C, but not interleukin-6 –174G/C, polymorphism associates with hypertension in rheumatoid arthritis
1Department of Rheumatology, Dudley Group of Hospitals NHS Trust, Russells Hall Hospital, Dudley, UK, 2Department of Internal Medicine, School of Medicine, University of Ioannina, Ioannina, Greece, 3Department of Clinical Biochemistry, Dudley Group of Hospitals NHS Trust, Russells Hall Hospital, Dudley, 4Wolfson Computer Laboratory, University Hospital Birmingham NHS Foundation Trust, Birmingham and 5ARC Epidemiology Unit, University of Manchester, Manchester, UK.
Correspondence to:
G. D. Kitas, Department of Rheumatology, Dudley Group of Hospitals NHS Trust, Russells Hall Hospital, Pensnett Road, Dudley, West Midlands, DY1 2HQ, UK. E-mail: gd.kitas{at}dgoh.nhs.uk or g.d.kitas{at}bham.ac.uk
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Abstract |
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Objectives. Part of the deleterious effects of systemic inflammation on the cardiovascular system of patients with RA may be exerted via increased propensity to hypertension. IL-6 and TGF-β1 are important regulators of the inflammatory response. In some, but not all, studies, IL6 –174G/C (rs1800795) and TGFB1 869T/C (rs1982073) gene polymorphisms have been associated with hypertension in the general population. The present study addressed their potential association with hypertension in RA patients.
Methods. TGFB1 869T/C and IL6 –174G/C were identified in 400 RA patients and 422 local, non-RA controls using real-time PCR and melting curve analysis. Binary logistic and linear regression models were used to identify the independence of the effects of the polymorphisms on hypertension.
Results. Genotypic and allelic frequencies of the two polymorphisms were similar in RA and controls. Within the RA group, there was no significant association between IL6 –174G/C and hypertension, but TGF 869T-allele carriers had significantly increased prevalence of hypertension compared with CC homozygotes (70.2 vs 55.2%; P = 0.023). This association remained significant after adjustment for other hypertension risk factors and medication (odds ratio = 1.96; 95% CI 1.02, 3.77; P = 0.044), and was more pronounced in patients with increased systemic inflammation.
Conclusions. This study suggests an association of TGFB1 869T/C, but not of IL6 –174G/C, with hypertension in RA patients. If this finding is confirmed in prospective studies, this polymorphism could be used as a screening tool for RA patients with higher risk of developing hypertension and lead to increased surveillance and earlier treatment.
KEY WORDS: Rheumatoid arthritis, Hypertension, Genetics, Gene, Transforming growth factor, Interleukin
Submitted 9 June 2008;
revised version accepted 23 October 2008.
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