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From the National Heart, Lung, and Blood Institute's Framingham
Heart Study (C.J.O., M.G.L., D.L.), Framingham, Mass; the Cardiac Unit
(C.J.O.), Department of Medicine, Massachusetts General Hospital, the
Divisions of Cardiology and Clinical Epidemiology, Beth Israel Hospital
(D.L.), the Department of Cardiology, Children's Hospital (K.L.), and
the Cardiovascular Division, Department of Medicine, Brigham and Women's
Hospital (K.L., V.S.R.), Harvard Medical School, Boston, Mass; the Molecular
Biology Section, Lipid Metabolism Laboratory, Jean Mayer US Department of
Agriculture Human Nutrition Research Center on Aging at Tufts University
(J.M.O., E.J.S.), Boston, Mass; the Departments of Neurology (R.H.M.),
Preventive Medicine and Epidemiology (M.G.L., D.L.), Boston University School
of Medicine, Boston, Mass; and the National Heart, Lung, and Blood Institute,
National Institutes of Health (C.J.O., D.L.), Bethesda, Md.
Correspondence to Christopher J. O'Donnell, MD, MPH, Framingham Heart Study, 5 Thurber St, Framingham, MA 01701. E-mail chris{at}fram.nhlbi.nih.gov
Background—There is controversy
regarding the association of the angiotensin-converting
enzyme deletion-insertion (ACE D/I) polymorphism
with systemic hypertension and with blood pressure. We investigated
these relations in a large population-based sample of men and women by
using association and linkage analyses.
Methods and Results—The study sample consisted of 3095
participants in the Framingham Heart Study. Blood pressure measurements
were obtained at regular examinations. The ACE D/I
polymorphism was identified by using a polymerase chain reaction
assay. In logistic regression analysis, the adjusted odds
ratios for hypertension among men for the DD and
DI genotypes were 1.59 (95% confidence interval
[CI], 1.13 to 2.23) and 1.18 (95% CI, 0.87 to 1.62), respectively,
versus II (
Conclusions—In our large, population-based sample, there is
evidence for association and genetic linkage of the ACE
locus with hypertension and with diastolic blood pressure
in men but not women. Our data support the hypothesis that
ACE, or a nearby gene, is a sex-specific candidate gene
for hypertension. Confirmatory studies in other large population-based
samples are warranted.
© 1998 American Heart Association, Inc.
Clinical Investigation and Reports
Evidence for Association and Genetic Linkage of the Angiotensin-Converting Enzyme Locus With Hypertension and Blood Pressure in Men but Not Women in the Framingham Heart Study
2 P=.02). In
women, adjusted odds ratios for the DD and
DI genotypes were 1.00 (95% CI, 0.70 to 1.44)
and 0.78 (95% CI, 0.56 to 1.09), respectively (P=.14).
In linear regression analysis, there was an association of the
ACE DD genotype with increased
diastolic blood pressure in men (age-adjusted
P=.03, multivariate-adjusted
P=.14) but not women. Quantitative trait linkage
analyses in 1044 pairs of siblings, by using both ACE
D/I and a nearby microsatellite polymorphism of the human
growth hormone gene, supported a role of the ACE locus
in influencing blood pressure in men but not in women.
Key Words: angiotensin • trials • genetics • genes • hormones • hypertension • blood pressure
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S. T. Turner, E. Boerwinkle, and C. F. Sing Context-Dependent Associations of the ACE I/D Polymorphism With Blood Pressure Hypertension, October 1, 1999; 34(4): 773 - 778. [Abstract] [Full Text] [PDF]
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E. G. BURCHARD, E. K. SILVERMAN, L. J. ROSENWASSER, L. BORISH, C. YANDAVA, A. PILLARI, S. T. WEISS, J. HASDAY, C. M. LILLY, J. G. FORD, et al. Association Between a Sequence Variant in the IL-4 Gene Promoter and FEV1 in Asthma Am. J. Respir. Crit. Care Med., September 1, 1999; 160(3): 919 - 922. [Abstract] [Full Text]
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M. A. VAN DIJK, D. J.M. PETERS, M. H. BREUNING, and P. C. CHANG The Angiotensin-Converting Enzyme Genotype and Microalbuminuria in Autosomal Dominant Polycystic Kidney Disease J. Am. Soc. Nephrol., September 1, 1999; 10(9): 1916 - 1920. [Abstract] [Full Text]
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J. Baima, M. Nicolaou, F. Schwartz, A. L. DeStefano, A. Manolis, I. Gavras, C. Laffer, F. Elijovich, L. Farrer, C. T. Baldwin, et al. Evidence for Linkage Between Essential Hypertension and a Putative Locus on Human Chromosome 17 Hypertension, July 1, 1999; 34(1): 4 - 7. [Abstract] [Full Text] [PDF]
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F. Perticone, R. Maio, C. Cosco, R. Ceravolo, S. Iacopino, M. Chello, P. Mastroroberto, D. Tramontano, and P. L Mattioli Hypertensive left ventricular remodeling and ACE-gene polymorphism Cardiovasc Res, July 1, 1999; 43(1): 192 - 199. [Abstract] [Full Text] [PDF]
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R. J. van SUYLEN, E. F. WOUTERS, H. J. PENNINGS, E. C. CHERIEX, P. E. van POL, A. W. AMBERGEN, A.-M. VERMELIS, and M. J. DAEMEN The DD Genotype of the Angiotensin Converting Enzyme Gene Is Negatively Associated with Right Ventricular Hypertrophy In Male Patients with Chronic Obstructive Pulmonary Disease Am. J. Respir. Crit. Care Med., June 1, 1999; 159(6): 1791 - 1795. [Abstract] [Full Text]
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C. J. O'Donnell and W. B. Kannel Is There a Racial Predisposition to Hypertension? Hypertension, November 1, 1998; 32(5): 817 - 819. [Full Text] [PDF]
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 ACE Gene for Hypertension May Be Sex-Specific Journal Watch Cardiology, July 10, 1998; 1998(710): 5 - 5. [Full Text]
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 ACE Gene for Hypertension May Be Sex-Specific Journal Watch Women's Health, July 1, 1998; 1998(701): 5 - 5. [Full Text]
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F. Soubrier Blood Pressure Gene at the Angiotensin I–Converting Enzyme Locus : Chronicle of a Gene Foretold Circulation, May 19, 1998; 97(18): 1763 - 1765. [Full Text] [PDF]
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M. Fornage, C. I. Amos, S. Kardia, C. F. Sing, S. T. Turner, and E. Boerwinkle Variation in the Region of the Angiotensin-Converting Enzyme Gene Influences Interindividual Differences in Blood Pressure Levels in Young White Males Circulation, May 19, 1998; 97(18): 1773 - 1779. [Abstract] [Full Text] [PDF]
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