From the Division of Cardiology (M.K., P.K., J.V.), Department of
Medicine, Helsinki University Central Hospital, Helsinki, Finland; Institute
of Biomedicine and Physiology (A.H., L.L.), University of Helsinki, Finland;
and Department of Pediatrics (H.N., P.C.W.), University of Texas Southwestern
Medical Center (Dallas).
Background—Aldosterone
has direct and indirect effects on the heart, and genetic variations in
aldosterone synthesis could therefore influence 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.
Methods and Results—A Finnish population sample of 84 persons (44
women) aged 36 to 37 years was studied by M-mode and Doppler
echocardiography to assess left
ventricular size, mass, and function. Subjects were
genotyped through the use of the polymerase chain reaction for
two diallelic polymorphisms in CYP11B2: one in the
transcriptional regulatory region (promoter) and the other in the
second intron. In multiple regression analyses, the
CYP11B2 promoter genotype predicted
statistically significant variations in left ventricular
end-diastolic diameter (ß=.40, P<.0001),
end-systolic diameter (ß=.33, P=.0009), and
mass (ß=.17, P=.023). These effects were independent
of potentially confounding factors, including sex, body size, blood
pressure, physical activity, smoking, and ethanol consumption.
Genotype groups also differed in a measure of left
ventricular diastolic function, the heart
rate–adjusted atrial filling fraction (P=.018).
Increased dietary salt, which is known to predict increased left
ventricular mass, had this effect only in association with
certain CYP11B2 genotypes
(P<.001).
Conclusions—Genetic variations in or near the
aldosterone synthase (CYP11B2) gene strongly
affect left ventricular size and mass in young adults free
of clinical heart disease. These polymorphisms may also influence
the response of the left ventricle to increases in dietary salt.
© 1998 American Heart Association, Inc.
Clinical Investigation and Reports
Associations Between Human Aldosterone Synthase (CYP11B2) Gene Polymorphisms and Left Ventricular Size, Mass, and Function
Key Words: ventricles • echocardiography • genes
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