Genetic polymorphisms of the angiotensin II type 1 (AT1) receptor gene.

Numerous essential, physiological effects on the cardiovascular system are attributable to angiotensin II (Ang II). Because of this we can assume that genetic changes in the specific receptor of Ang II (Ang II type 1 receptor gene, AT1) play a decisive role in the occurrence of cardiovascular disease associated with blood pressure regulation, vascular tone, cardiac and vascular growth process. To test this hypothesis, we examined the presence of polymorphisms within the coding region of the AT1 gene using polymerase chain reaction (PCR) and subsequent non-radioactive sequencing of samples from a control group with no previous history of cardiovascular complaint in individuals or immediate family. Using the Taq-sequencing procedure we found polymorphic sites, especially in the 5' region of the gene (base pair positions 9, 16, 87, 133, 186), two of which led to an exchange of the amino acid (amino acid 6: Ser<==>Pro, amino acid 45: Gly<==>Arg). Together with the silent polymorphism at base pair position 573, which our group established previously, an additional polymorphism in the 3' region of the gene was discovered. This, however, did not confer any changes in amino acid sequence. In a preliminary study we found no association between the distribution of the C/T573 polymorphic site and cardiovascular disease, such as essential hypertension (n = 20) coronary artery disease (n = 16) hypertrophic cardiomyopathy (n = 12) or dilated cardiomyopathy (n = 21). Further studies will be needed to determine to what extent the polymorphisms described are associated with cardiovascular disease.