From INSERM U358, Hôpital Saint-Louis, Paris, France (E.B., N.C.,
F.S.); the Division of Nephrology and Hypertension, San Raffaele Hospital,
University of Milan, Italy (L.C.); the Department of Clinical Pharmacology, St
Bartholomew's Hospital, London (M.C.); the Wellcome Trust Center for
Human Genetics, Oxford (B.K.); the Department of Medicine and Therapeutics,
Western Infirmary, Glasgow (J.C.), UK; the Department of Epidemiology and
Biostatistics, Erasmus University Medical School, Rotterdam, Netherlands
(D.G.); the Department of Internal Medicine, University of Heidelberg (S.S.);
the Department of Internal Medicine, University of Regensburg (H. Schunkert);
the Department of Internal Medicine, Franz-Volhard-Clinic, Humboldt University
(H. Schuster), and the Department of Internal Medicine, University Clinic
Benjamin Franklin (A.M.S., E.B.), Berlin, Germany.
Correspondence to Florent Soubrier, INSERM U358, Hôpital Saint-Louis, 1, Ave Claude Vellefaux, 75475 Paris, cedex 10, France. E-mail Soubrier{at}inserm.chu-stlouis.fr
Abstract—Different family and
case-control studies support genetic linkage and association at the
human angiotensinogen (AGT) locus with
essential hypertension. To extend these previous observations, a
European collaborative study of nine centers was set up to create a
large resource of affected sibling pairs. The AGT locus was
studied using a highly polymorphic dinucleotide repeat
in the 3'-flanking region of the gene in 350 European families,
comprising 630 affected sibling pairs. Statistical analyses
using two different methods did not show any evidence for linkage
either in the whole panel or in family subsets selected for severity or
early onset of disease. Although several arguments from association
studies suggest a role of the AGT gene in essential
hypertension, this large family study did not replicate the initial
linkage reported in smaller studies. Our results highlight the
difficulty of identifying susceptibility genes by linkage
analysis in complex diseases.
© 1998 American Heart Association, Inc.
Scientific Contributions
Evaluation of the Angiotensinogen Locus in Human Essential Hypertension
A European Study
Key Words: angiotensinogen • hypertension, essential • genetics • microsatellite repeats
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