血管紧张素转换酶2基因型与厄贝沙坦改善高血压患者左室重构及功能的关系

Relationship Between the Angiotensin-Converting Enzyme 2 Genotype and Effect of Irbesartan on Left Ventricular Structure and Function in Hypertensive Patients

背景一些研究结果提示血管紧张素转换酶2(ACE2)具有调节心脏结构和功能的作用,ACE2基因多态性与左室结构和功能相关,但 ACE2基因型对降压药物改善高血压患者的左室重构和功能是否有影响,目前尚不清楚。目的观察 ACE2基因 G9570A 多态性与厄贝沙坦影响高血压患者左室结构及功能的相关性。方法选择坐位收缩压<180 mmHg 和(或)舒张压90～109 mmHg 无血缘关系的汉族原发性高血压患者395例(男性205例,女性190例),均服用厄贝沙坦治疗,起始剂量150 mg/d,治疗4周后血压未达到有效标准者药量加倍,共观察48周。应用聚合酶链反应和限制性片段长度多态性(PCR-RFLP)的方法检测 ACE2基因 G9570A 多态性,并随机抽取20份标本进行基因测序以核实基因分型。按性别分组分析降压幅度及左室结构和功能各参数的改变值与基因型的关系。结果经过48周厄贝沙坦治疗,所有患者血压明显下降(P<0.01)。不同亚组间血压下降幅度无统计学意义(P>0.05)。携带 A 等位基因患者左室质量和左室质量指数下降幅度及心脏功能改善程度显著高于其他亚组(P<0.05)。结论 ACE2基因型与左室质量指数下降值有关。ACE2基因多态性对高血压心脏结构和功能损害的患者降压药物的选择有一定的参考价值,但需进一步深入研究。

Background Experimental data have shown that polymorphisms in the angiotensin-converting enzyme 2 （ACE2） gene are related to echocardiographically determined parameters of left ventricular mass, structure or function in the general population whether ACE2 genotype influences the effect of angiotensin Ⅱ receptor blocker which improve left ventricular remodeling and function is unknown. Objective To investigate the association between ACE2 gene G9570A polymorphism and the effect of irbesartan on left ventricular structure and function in hypertensive patients. Methods Two hundred and five male patients and 190 female patients who were preliminaryly diagnosised with mild and moderate essential hypertension were treated with irbesartan for 48 weeks with initial dose of 150 mg/d and titrated to 300 mg/d to reach the targed BP. Gene polymorphisms of ACE2 G9570A were detected by PCR-RFLP methods. The association between changes in the SBP, DBP, parameters of left ventricular structure and function and genotypes of the ACE2 gene locus were analyzed. Results Irbesartan reducted in blood pressure in all patients（P〈0. 01）. The decreased magnitude of left ventricular mass（LVM）, left ventricular mass index（LVMI） and the improvement of parameters of left ventricular function is greater in patients carrying only A allele than those carrying G allele（ P〈0.05）. Conclusion The ACE2＇s genotypes are related to improvement of LVMI. The further investigation on the effect of G9570A polymorphism of ACE2 gene on the responses to angiotensin Ⅱ receptor is warranted.