Ann. Hum. Genet. (1999), 63, 369–374 Printed in Great Britain 369 SHORT COMMUNICATION Characterization of polymorphisms in the promoter of the human angiotensin II subtype 1 (AT1) receptor gene * J. ERDMANN, * K. RIEDEL, K. ROHDE, I. FOLGMANN, T. WIENKER, E. FLECK  V. REGITZ-ZAGROSEK  Department of Internal Medicine and Cardiology, Charite  , Humboldt University and Deutsches Herzzentrum Berlin, Germany  Max-Delbru  ck-Centrum for Molecular Medicine, Department of Bioinformatics, Berlin-Buch, Germany  Institute of Medical Statistics, University of Bonn, Germany  In this study eight sequence variants in the functional promoter of the human angiotensin II subtype 1 (AT1 or AGTR1) receptor gene are reported. Six of these variants are in nearly total linkage disequilibrium with each other and occur with a frequency of 157 %. By haplotype estimation this group of eight sequence variants is characterized by only five haplotypes. There is no linkage disequilibrium between one of these haplotypes and the AT11166AC variant. The finding of polymorphic sites in the functional promoter of the human AT1 locus will be beneficial to the study of the role of the AT1 receptor gene in hypertension and other cardiovascular diseases.  The renin–angiotensin system is an important component of blood pressure regulation, playing roles in saltwater homeostasis and vascular tone, and has been suspected to be involved in hypertension. Angiotensin II receptors (ATR), which mediate the vasoconstrictive and salt- conserving actions of the renin–angiotensin sys- tem, represent interesting candidate genes for cardiovascular diseases. Two subtypes of cell surface receptors have been identified (AT1 and AT2) based on their different binding affinities for subtype-specific compounds (Bumpus et al. 1991 ; Timmermans et al. 1993). AT1 is a G-protein coupled receptor with seven * J. Erdmann and K. Riedel contributed equally to the work. Correspondence : Jeanette Erdmann, Deutsches Herzzentrum Berlin, Forschungshaus 37, Augusten- burger Platz 1, D-13353 Berlin. Tel : 49 30 450 59298 ; Fax: 49 30 450 59998 ; E-mail : jeanette.erdmanncharite.de transmembrane domains (Murphy et al. 1991; Sasaki et al. 1991) and angiotensin II binding epitopes located in the N-terminus of the re- ceptor protein (Hjorth et al. 1994). The human AT1 gene (approved symbol AGTR1) was cloned in 1992 (Bergsma et al. 1992) and is present as a single-copy gene on human chromosome 3q21–q25 (Curnow et al. 1992). The gene spans at least 60 kb and comprises 5 exons. The entire coding region is located within exon 5 (Su et al. 1994, Guo et al. 1994). A genomic clone contain- ing 25 kb of the 5-flanking region has previously been shown to contain a functional promoter using chloramphenicol acetyltransferase (CAT) gene assays (Takayanagi et al. 1994). In the last years several groups have screened the coding and 3 untranslated region of the AT1 gene for genetic variants. The sequence changes described (573TC, 1062AG, 1166AC, 1517GT and 1878AG) do not alter the encoded amino acid sequence (Bonnardeaux et