Variation in the Region of the Angiotensin-Converting
Enzyme Gene Influences Interindividual Differences
in Blood Pressure Levels in Young White Males
Fornage M, Amos CI, Kardia S, Sing CF, Turner ST, Boerwinkle E
Human Genetics Center, University of Texas at Houston Health Science Center,
77225, USA.
Circulation, 97(18):1773-1779 (1998)
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.
Variance component linkage analysis