Department of Clinical Biochemistry, Herlev University Hospital, University of Copenhagen, Herlev, Denmark.
Pharmacogenet Genomics. 2010 Feb;20(2):77-85. doi: 10.1097/FPC.0b013e328333f70b.
This pharmacogenetics substudy from the Losartan Intervention for Endpoint reduction in Hypertension study in patients with hypertension and left ventricular hypertrophy (LVH) treated with the angiotensin receptor blocker losartan versus the beta-blocker atenolol for 4.8 years tested whether the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene and 12 other previously well-characterized polymorphisms of hypertension susceptibility genes affected blood pressure reduction, heart rate reduction, cardiovascular events, and/or response to treatment. These polymorphisms were chosen because they could affect blood pressure control or the pharmacological action of losartan or atenolol.
We genotyped 3503 patients, 1774 on losartan and 1729 on atenolol.
ACE and the 12 other genotypes did not affect the reduction in systolic blood pressure, diastolic blood pressure, pulse pressure, mean arterial pressure, or heart rate, or treatment differences between losartan and atenolol on these endpoints, as assessed by general linear models. Also, ACE and the 12 other genotypes did not affect risk of the primary composite endpoint or its components stroke, myocardial infarction, and cardiovascular death, or treatment differences between losartan and atenolol on these endpoints, as assessed by Cox proportional hazards models including baseline Framingham risk score and LVH.
ACE insertion/deletion and 12 other polymorphisms of hypertension susceptibility genes did not affect blood pressure reduction, heart rate reduction, or cardiovascular events in patients with hypertension and LVH, or treatment differences between losartan and atenolol on these endpoints. These results suggest that the observed effects of losartan versus atenolol in the Losartan Intervention for Endpoint reduction in hypertension study do not depend on ACE and 12 other polymorphisms of hypertension susceptibility genes.
这项来自高血压和左心室肥厚（LVH）患者的洛沙坦干预终点降低高血压研究的遗传药理学子研究，使用血管紧张素受体阻滞剂洛沙坦与β受体阻滞剂阿替洛尔治疗 4.8 年，检验血管紧张素转换酶（ACE）基因插入/缺失（I/D）多态性和其他 12 个先前已充分描述的高血压易感性基因多态性是否影响血压降低、心率降低、心血管事件和/或治疗反应。选择这些多态性是因为它们可能影响血压控制或洛沙坦或阿替洛尔的药物作用。
我们对 3503 名患者进行了基因分型，其中 1774 名服用洛沙坦，1729 名服用阿替洛尔。
ACE 和其他 12 种基因型并未影响收缩压、舒张压、脉压、平均动脉压或心率的降低，也未影响洛沙坦和阿替洛尔在这些终点上的治疗差异，这是通过一般线性模型评估的。同样，ACE 和其他 12 种基因型也不影响主要复合终点或其组成部分中风、心肌梗死和心血管死亡的风险，也不影响洛沙坦和阿替洛尔在这些终点上的治疗差异，这是通过包括基线 Framingham 风险评分和 LVH 的 Cox 比例风险模型评估的。
ACE 插入/缺失和其他 12 种高血压易感性基因多态性并未影响高血压和 LVH 患者的血压降低、心率降低或心血管事件，也未影响洛沙坦和阿替洛尔在这些终点上的治疗差异。这些结果表明，洛沙坦干预终点降低高血压研究中观察到的洛沙坦与阿替洛尔的作用不依赖于 ACE 和其他 12 种高血压易感性基因多态性。
