From the Human Genetics Center (M.F., E.B.) and the Institute of
Molecular Medicine (E.B.), University of Texas at Houston Health Science
Center; the Department of Epidemiology, University of Texas M.D. Anderson
Cancer Center, Houston (C.I.A.); the Department of Human Genetics, University
of Michigan, Ann Arbor (S.K., C.F.S.); and the Division of Hypertension,
Department of Internal Medicine, Mayo Clinic, Rochester, Minn (S.T.T.).
Correspondence to Eric Boerwinkle, PhD, Human Genetics Center, University of Texas Houston Health Science Center, PO Box 20334, Houston, TX 77225.
Abstract
Background—The
renin-angiotensin system regulates blood pressure through
its effects on vascular tone, renal hemodynamics, and
renal sodium and fluid balance.
Methods and Results—Using data from a large population-based
sample of 1488 siblings having a mean age of 14.8 years and belonging
to the youngest generation of 583 randomly ascertained three-generation
pedigrees from Rochester, Minn, we carried out variance
components–based linkage analyses to evaluate the contribution
of variation in four renin-angiotensin system gene regions
(angiotensinogen, renin, angiotensin
I–converting enzyme, and angiotensin II receptor type 1)
to interindividual variation in systolic,
diastolic, and mean arterial pressure. We
rejected the null hypothesis that allelic variation in the region of
the angiotensin-converting enzyme (ACE) gene
does not contribute to interindividual blood pressure variability.
After conditioning on measured covariates, variation in this region
accounted for 0%, 13% (P=0.04), and 16%
(P=0.04) of the interindividual variance in
systolic, diastolic, and mean arterial
pressures, respectively. These estimates were even greater in a subset
of subjects with a positive family history of hypertension (0%, 29%
[P=0.005], and 32% [P<0.005],
respectively). In sex-specific analyses, genetic variation in
the region of the ACE gene significantly influenced
interindividual blood pressure variation in males (37% for SBP
[P=0.03], 38% for DBP [P=0.04], and
53% for MAP [P<0.005]) but not in females.
Conclusions—Although it is possible that variation in a gene near
the ACE gene may explain the observed results, knowledge
about the physiological involvement of ACE in blood
pressure regulation supports the proposition that the
ACE gene itself influences blood pressure variability in
a sex-specific manner.
© 1998 American Heart Association, Inc.
Clinical Investigation and Reports
Variation in the Region of the Angiotensin-Converting Enzyme Gene Influences Interindividual Differences in Blood Pressure Levels in Young White Males
Key Words: linkage analysis • blood pressure • angiotensin-converting enzyme • whites • males
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