Dhamrait Sukhbir S, Payne John R, Li Ping, Jones Alun, Toor Iqbal S, Cooper Jacqueline A, Hawe Emma, Palmen Jutta M, Wootton Peter T E, Miller George J, Humphries Steve E, Montgomery Hugh E
Centre for Cardiovascular Genetics, British Heart Foundation Laboratories, Royal Free & University College London Medical School, Rayne Building, London, UK.
Eur Heart J. 2003 Sep;24(18):1672-80. doi: 10.1016/s0195-668x(03)00441-x.
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.
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).
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.
激肽在血管紧张素I转换酶（ACE）抑制降低心血管风险的有益作用中的贡献仍不清楚。激肽诱导型B1受体（B(1)R）和组成型B2受体（B(2)R）的基因包含功能性变体：B(1)R-699C（而非G）和B(2)R(-9)（而非+9）等位基因与更高的mRNA表达相关，B(2)R(-9)等位基因与左心室肥厚反应降低相关。我们在一项大型前瞻性研究中测试了这些基因变体是否影响高血压患者的冠状动脉风险。
对2706名既往健康的英国男性（招募时平均年龄56岁；中位随访10.8年）进行激肽受体变体基因分型。仅在B(1)R-699GG纯合子（风险比2.14 [1.42 - 3.22]；P<0.0001）和B(2)R(+9,+9)个体（风险比3.51 [1.69 - 7.28]；P = 0.001）中，收缩期高血压（收缩压≥160 mmHg）所致的冠状动脉风险显著更高，而在B(1)R-699C等位基因携带者（风险比0.82 [0.28 - 2.42]；P = 0.76）或B(2)R(-9,-9)纯合子（风险比1.25 [0.51 - 3.04]；P = 0.63）中并非如此。
激肽B(1)和B(2)受体基因的常见变异影响前瞻性高血压患者的冠状动脉风险。这些是首次报道的表明B(1)R在人类冠状动脉疾病中起作用的人体数据，也是首次证明B(2)R有类似作用的前瞻性研究。
