Variation in bradykinin receptor genes increases the cardiovascular risk associated with hypertension.

Autor:	Dhamrait SS; Centre for Cardiovascular Genetics, British Heart Foundation Laboratories, Royal Free & University College London Medical School, Rayne Building, London, UK., Payne JR, Li P, Jones A, Toor IS, Cooper JA, Hawe E, Palmen JM, Wootton PT, Miller GJ, Humphries SE, Montgomery HE
Jazyk:	angličtina
Zdroj:	European heart journal [Eur Heart J] 2003 Sep; Vol. 24 (18), pp. 1672-80.
DOI:	10.1016/s0195-668x(03)00441-x
Abstrakt:	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 (B(1)R) and constitutive B2 receptor (B(2)R) contain functional variants: the B(1)R-699C (rather than G) and the B(2)R(-9) (rather than +9) alleles are associated with greater mRNA expression and the B(2)R(-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>/=160 mmHg) was significantly higher only in B(1)R-699GG homozygotes (HR 2.14 [1.42-3.22]; P<0.0001) and B(2)R(+9,+9) individuals (HR 3.51 [1.69-7.28]; P=0.001) but not in B(1)R-699C allele carriers (HR 0.82 [0.28-2.42]; P=0.76) or in B(2)R(-9,-9) homozygotes (HR 1.25 [0.51-3.04]; P=0.63). Conclusions: Common variation in the genes for the kinin B(1)and B(2)receptors influences prospective hypertensive coronary risk. These are the first reported human data to suggest a role for the B(1)R in human coronary vascular disease, and the first prospective study to demonstrate a similar role for the B(2)R.
Databáze:	MEDLINE
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