Bis Joshua C, Smith Nicholas L, Psaty Bruce M, Heckbert Susan R, Edwards Karen L, Lemaitre Rozenn N, Lumley Thomas, Rosendaal Frits R
Cardiovascular Health Research Unit, Department of Epidemiology, University of Washington, Seattle, Washington 98101, USA.
Am J Hypertens. 2003 Dec;16(12):1011-7. doi: 10.1016/j.amjhyper.2003.07.018.
The ThrThr genotype of the angiotensinogen (AGT) Met235Thr polymorphism has been associated with elevated AGT levels, hypertension, increased heart disease risk, and improved blood pressure (BP) response to angiotensin-converting enzyme (ACE) inhibitors. We hypothesized that risk of stroke or myocardial infarction (MI) associated with ACE inhibitor use varies by AGT genotype, with a larger protective effect of ACE inhibitors in individuals with the ThrThr genotype than individuals who are carriers of the Met allele.
We conducted a population-based case-control study. Participants were health maintenance organization members aged 30 to 79 years with treated hypertension. Those who survived incident stroke (n = 116) or MI (n = 208) during the study period were designated as cases. Control subjects (n = 717) were randomly sampled and frequency-matched to MI cases on age, sex, and calendar year. Health history, medication use, and AGT genotype were assessed.
ThrThr genotype was present in 21% of stroke cases, 26% of MI cases, and 19% of control subjects. Compared with nonuse, ACE inhibitor use was associated with lower stroke risk among Thr homozygotes (odds ratio [OR] = 0.37, 95% CI = 0.14 to 0.99) than among Met carriers (OR = 1.4, 95% CI = 0.88 to 2.4; P for interaction =.02). Compared with nonuse, ACE inhibitor use was associated with similar MI risk among Thr homozygotes (OR = 0.90, 95% CI = 0.62 to 1.3) and among Met carriers (OR = 1.2, 95% CI = 0.60 to 2.5; P for interaction = 0.5).
In this hypertensive population, the association of ACE inhibitor use with risk of nonfatal stroke varied by genotype. The protective association between ACE inhibitor use and nonfatal stroke risk among individuals with ThrThr genotype was not observed for nonfatal MI.
血管紧张素原（AGT）Met235Thr多态性的ThrThr基因型与AGT水平升高、高血压、心脏病风险增加以及对血管紧张素转换酶（ACE）抑制剂的血压（BP）反应改善有关。我们假设，与ACE抑制剂使用相关的中风或心肌梗死（MI）风险因AGT基因型而异，ACE抑制剂对ThrThr基因型个体的保护作用大于Met等位基因携带者。
我们进行了一项基于人群的病例对照研究。参与者为年龄在30至79岁、患有高血压且接受治疗的健康维护组织成员。在研究期间发生中风（n = 116）或MI（n = 208）且存活的患者被指定为病例。对照对象（n = 717）通过随机抽样，并在年龄、性别和历年方面与MI病例进行频率匹配。评估健康史、药物使用情况和AGT基因型。
ThrThr基因型在21%的中风病例、26%的MI病例和19%的对照对象中存在。与未使用ACE抑制剂相比，ACE抑制剂的使用与Thr纯合子中风风险较低相关（优势比[OR] = 0.37，95%置信区间[CI] = 0.14至0.99），而在Met携带者中则较高（OR = 1.4，95% CI = 0.88至2.4；交互作用P值 = 0.02）。与未使用ACE抑制剂相比，ACE抑制剂的使用与Thr纯合子MI风险相似（OR = 0.90，95% CI = 0.62至1.3），在Met携带者中也是如此（OR = 1.2，95% CI = 0.60至2.5；交互作用P值 = 0.5）。
在这个高血压人群中，ACE抑制剂使用与非致命性中风风险的关联因基因型而异。在非致命性MI中，未观察到ACE抑制剂使用与ThrThr基因型个体非致命性中风风险之间的保护关联。
