(Hypertension. 1999;33:844-849.)
© 1999 American Heart Association, Inc.
Scientific Contribution |
Evidence for Involvement of the Type 1 Angiotensin II Receptor Locus in Essential Hypertension
From the Departments of Medicine (K. Kainulainen, K. Kontula), Medical Genetics (L.P., M.P), and Public Health (J.K.), University of Helsinki; the Departments of Human Molecular Genetics (M.P., L.P., A.-C.S.) and Epidemiology and Health Promotion (E.V.), National Public Health Institute, Helsinki, Finland; the Department of Public Health (M.K.), University of Turku (Finland); and the Department of Psychiatry and Columbia Genome Center (J.T.), Columbia University, New York, NY.
Abstract—Components of the
renin-angiotensin system play an important role in the
normal regulation of blood pressure. We carried out a comprehensive
genetic linkage study of the genes involved in the
renin-angiotensin cascade in Finnish hypertensive twins and
their affected siblings. We found no evidence for linkage between
essential hypertension and the genes coding for renin,
angiotensinogen, angiotensin-converting enzyme,
or kallikrein 1 in the 329 hypertensive individuals of 142 families
studied. In contrast, two intragenic markers for the type 1
angiotensin II receptor (AT1) showed some
evidence for linkage in the total sample. A closer examination of this
gene locus was carried out using subgroups of nonobese sibpairs with
early onset of hypertension and uniform geographical origin. These
stratifications yielded suggestive evidence for linkage of hypertension
to the genetic area containing the AT1 gene, with a maximal
multipoint logarithm of the odds (LOD) score of 2.9. A genetic
association study carried out in an independent series of 50
hypertensive cases and 122 normotensive controls showed an increase in
the frequency of the A1166
C allele of the AT1 gene
in the hypertensive individuals. In a novel variant of model-free
multipoint linkage analysis allowing linkage disequilibrium in
the calculations, an LOD score of 5.13 was obtained. Sequence
analyses of the entire coding region and 848 bp of promoter
region in the DNA sample on 8 index samples did not reveal previously
unpublished sequence variations. The data provide evidence that a
common genetic variant of the AT1 gene locus influences the
risk of essential hypertension in the Finnish population.
Key Words: hypertension, essential • receptor, angiotensin II • siblings • linkage • Finnish population
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