Association of ACE2 Genetic Variants With Blood Pressure, Left Ventricular Mass, and Cardiac Function in Caucasians With Type 2 Diabetes

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.