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(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

Katariina Kainulainen; Markus Perola; Joseph Terwilliger; Jaakko Kaprio; Markku Koskenvuo; Ann-Christine Syvänen; Erkki Vartiainen; Leena Peltonen; Kimmo Kontula

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 A1166C 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the entire coding region and 848 bp of promoter region in the DNA sample on 8 index samples did not reveal previously unpublished sequence variations.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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