From the Department of Physiology, University of Melbourne, Parkville
(B.A.I., S.B.H.), and Clinical Hematology, Alfred Hospital, Prahran (M.K.K.),
Australia; and the Cardiovascular Research Center, Massachusetts General
Hospital-East, Charlestown, Mass (M.G.M., H.J.J.).
Correspondence to Professor Stephen B. Harrap, Department of Physiology, University of Melbourne, Parkville, Victoria 3052, Australia. E-mail s.harrap{at}physiology.unimelb.edu.au
Abstract—Cardiac
hypertrophy is a common but not inevitable complication of
hypertension. Variation in heart size in hypertensives may reflect
independent genetic susceptibility to cardiac hypertrophy.
Using an experimental genetic model, we determined the location of
quantitative trait loci responsible for cardiac hypertrophy
and/or hypertension. We studied 182 F2 male animals derived
from a cross of the spontaneously hypertensive rat and normotensive
Donryu rats. Direct mean arterial pressure (MAP) and left
ventricular (LV) mass were measured at 20 weeks of age, and
DNA was obtained for linkage analysis. The estimated
heritability of MAP was 62% and for LV mass expressed per unit of body
weight (relative LV mass) was 76%. We used 185 polymorphic
markers, with an average intermarker distance of 12.3 centimorgans for
a genome-wide scan in a representative subgroup of 46
animals to identify preliminary quantitative trait loci, which were
then mapped in all 182 male F2 rats. Two loci showed
logarithm of the odds scores of >4.0. One on chromosome 2,
Lvm-1, was linked to relative LV mass but showed no
evidence of linkage to MAP. Another locus on chromosome 1,
Map-1, was linked to MAP. In the same region, a locus
Lvm-2 was linked with relative LV mass. These data
indicate the existence of a genetic locus on chromosome 2 of the
spontaneously hypertensive rat that affects relative LV mass
independently of blood pressure.
© 1998 American Heart Association, Inc.
Scientific Contributions
Independent Genetic Susceptibility to Cardiac Hypertrophy in Inherited Hypertension
Key Words: genetics • blood pressure • hypertrophy, cardiac • genetics • rats, inbred SHR
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