GENETIC-ANALYSIS OF THE HUMAN TYPE-1 ANGIOTENSIN-II RECEPTOR

Angiotensin II is a potent pressor hormone and a primary regulator of aldosterone secretion. It acts through at least two types of receptors termed AT1 and AT2. We analyzed cDNA and genomic clones encoding the human angiotensin II type-1 receptor, AT1. The human AT1 gene was mapped to chromosome 3q by polymerase chain reaction analysis of DNA from a panel of human-hamster somatic cell hybrids. The predicted amino acid sequence is 95% identical to the corresponding rat and bovine receptors and 25% and 22% identical, respectively, to the receptors encoded by the RTA and MAS genes. Characterization of several human cDNA clones demonstrated the existence of two alternate 5'-untranslated regions (UTRs) that contain a common initial sequence but differ by the presence or absence of an insertion of 84 base pairs. In the genomic sequence, the coding sequences are contained in a single exon, with an intron occurring in the 5'-UTR at the position of insertion of the 84-base pair sequence. The exons encoding the alternate 5'-UTRs are located at least 3.8 kilobases away from the exon encoding the protein. Reverse transcription-polymerase chain reaction analysis showed that both forms of 5'-UTR are present in approximately equal abundance in a range of tissues expressing AT1. The reagents developed in this work may be useful in testing the hypothesis that genetic variations in angiotensin II receptor function are associated with a tendency to develop hypertension.