Department of Medicine, University of Melbourne, Austin Health, Victoria, Australia.
Am J Hypertens. 2012 Feb;25(2):216-22. doi: 10.1038/ajh.2011.188. Epub 2011 Oct 13.
Cardiovascular disease is common in diabetes, and is associated with activation of the renin-angiotensin system (RAS). Angiotensin-converting enzyme (ACE)2 is a recently described member of the RAS, and this study investigated whether ACE2 polymorphisms are associated with hypertension, left ventricular (LV) mass, and cardiac function in type 2 diabetes.
Variants in ACE2 (rs1978124, rs2074192, rs4240157, rs4646156, rs4646188) were examined in 503 Caucasian subjects with type 2 diabetes. As ACE2 is located on the X chromosome, analyses were performed separately for men and women. Hypertension was defined by a history of hypertension, and/or antihypertensive medications or blood pressure (BP) >130/80 mm Hg. LV mass and systolic function (ejection fraction) were assessed by transthoracic echocardiography.
In men, hypertension was more prevalent with the ACE2 rs2074192 C allele (P = 0.023), rs4240157 G allele (P = 0.016) and rs4646188 T allele (P = 0.006). In men, the rs1978124 A allele was associated with a significantly lower ejection fraction compared to the G allele (62.3 ± 13.3 vs. 67.2 ± 10.9%, P = 0.002). This association remained significant after covariate adjustment for age, body mass index, hypertension, antihypertensive treatment, and BP. In women, the prevalence of hypertension was higher (P = 0.009) with the rs4240157 G allele, and the rs1978124 A allele was associated with significantly higher LV mass (P = 0.008).
In Caucasians with type 2 diabetes, genetic variation in ACE2 is associated with hypertension and reduced systolic function in men, and hypertension and increased LV mass in women.
心血管疾病在糖尿病中很常见，与肾素-血管紧张素系统（RAS）的激活有关。血管紧张素转换酶（ACE）2 是最近描述的 RAS 成员，本研究调查了 ACE2 多态性是否与 2 型糖尿病患者的高血压、左心室（LV）质量和心功能有关。
在 503 名高加索 2 型糖尿病患者中检测了 ACE2（rs1978124、rs2074192、rs4240157、rs4646156、rs4646188）的变异。由于 ACE2 位于 X 染色体上，因此分别对男性和女性进行了分析。高血压的定义为高血压病史和/或使用降压药物或血压（BP）>130/80mmHg。通过经胸超声心动图评估 LV 质量和收缩功能（射血分数）。
在男性中，ACE2 rs2074192 C 等位基因（P=0.023）、rs4240157 G 等位基因（P=0.016）和 rs4646188 T 等位基因（P=0.006）与高血压的患病率较高相关。与 G 等位基因相比，男性的 rs1978124 A 等位基因与射血分数明显降低相关（62.3±13.3%比 67.2±10.9%，P=0.002）。这种关联在调整年龄、体重指数、高血压、降压治疗和 BP 等混杂因素后仍然显著。在女性中，rs4240157 G 等位基因与高血压的患病率较高相关（P=0.009），rs1978124 A 等位基因与 LV 质量明显增加相关（P=0.008）。
在 2 型糖尿病的高加索人群中，ACE2 的遗传变异与男性的高血压和收缩功能降低以及女性的高血压和 LV 质量增加有关。
