ASSOCIATIONS BETWEEN HUMAN ALDOSTERONE SYNTHASE (CYP11B2) GENE POLYMORPHISMS AND LEFT-VENTRICULAR SIZE, MASS, AND FUNCTION

Background-Aldosterone has direct and indirect effects on the heart, a nd genetic variations in aldosterone synthesis could therefore influen ce cardiac structure and function. Such variations might be associated with polymorphisms in the gene encoding aldosterone synthase (CYP11B2 ), the enzyme catalyzing the last steps of aldosterone biosynthesis, M ethods and Results-A Finnish population sample of 84 persons (44 women ) aged 36 to 37 years was studied by M-mode and Doppler echocardiograp hy to assess left ventricular size, mass, and function. Subjects were genotyped through the use of the polymerase chain reaction for two dia llelic polymorphisms in CYP11B2: one in the transcriptional regulatory region (promoter) and the other in the second intron. In multiple reg ression analyses, the CYP11B2 promoter genotype predicted statisticall y significant variations in left ventricular end-diastolic diameter (b eta=.40, P<.0001), end-systolic diameter (beta=.33, P=.0009), and mass (beta=.17, P=.023). These effects were independent of potentially con founding factors, including sex, body size, blood pressure, physical a ctivity, smoking, and ethanol consumption. Genotype groups also differ ed in a measure of left ventricular diastolic function, the heart rate -adjusted atrial filling fraction (P=.018). Increased dietary salt, wh ich is known to predict increased left ventricular mass, had this effe ct only in association with certain CYP11B2 genotypes (P<.001). Conclu sions-Genetic variations in or near the aldosterone synthase (CYP11B2) gene strongly affect left ventricular size and mass in young adults f ree of clinical heart disease. These polymorphisms may also influence the response of the left ventricle to increases in dietary salt.