Copyright © 2003 by the European Society of Cardiology.
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Variation in bradykinin receptor genes increases the cardiovascular risk associated with hypertension
a Centre for Cardiovascular Genetics, British Heart Foundation Laboratories, Royal Free & University College London Medical School, Rayne Building, London, UK
b Medical Research Council Cardiovascular Research Group, Wolfson Institute of Preventive Medicine, London, UK
* Correspondence to: Dr Hugh E. Montgomery, Portex Senior Lecturer in Cardiovascular Genetics, British Heart Foundation Laboratories, Royal Free & University College Medical School, Rayne Building, 5 University Street, London WC1E 6JF, UK. Tel: +44 (0)20 7679 6965; Fax: +44 (0)20 7679 6212
E-mail address: h.montgomery{at}ucl.ac.uk
Received 14 March 2003; revised 26 June 2003; accepted 9 July 2003
Aims The contribution of kinins to the beneficial effects of angiotensin I converting enzyme (ACE) inhibition in cardiovascular risk reduction remains unclear. The genes for the kinin inducible B1 receptor (B1R) and constitutive B2 receptor (B2R) contain functional variants: the B1R–699C (rather than G) and the B2R(–9) (rather than +9) alleles are associated with greater mRNA expression and the B2R(–9) allele with reduced left ventricular hypertrophic responses. We tested whether these gene variants influenced hypertensive coronary risk in a large prospective study.
Methods and results Two thousand, seven hundred and six previously healthy UK men (mean age at recruitment 56 years; median follow-up 10.8 years) were genotyped for the kinin receptor variants. The coronary risk attributable to systolic hypertension (SBP
160mmHg) was significantly higher only in B1R–699GG homozygotes (HR 2.14 [1.42–3.22]; P<0.0001) and B2R(+9,+9) individuals (HR 3.51 [1.69–7.28]; P=0.001) but not in B1R–699C allele carriers (HR 0.82 [0.28–2.42]; P=0.76) or in B2R(–9,–9) homozygotes (HR 1.25 [0.51-3.04]; P=0.63).
Conclusions Common variation in the genes for the kinin B1and B2receptors influences prospective hypertensive coronary risk. These are the first reported human data to suggest a role for the B1R in human coronary vascular disease, and the first prospective study to demonstrate a similar role for the B2R.
Key Words: Bradykinin • receptor • polymorphism • hypertension • risk • coronary disease
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