GENETIC POLYMORPHISMS OF THE ANGIOTENSIN-II TYPE-1 (AT(1)) RECEPTOR GENE

Numerous essential, physiological effects on the cardiovascular system are attributable to angiotensin II (Ang II). Because of this we can a ssume that genetic changes in the specific receptor of Ang II (Ang II type I receptor gene, AT) play a decisive role in the occurrence of ca rdiovascular disease associated with blood pressure regulation, vascul ar tone, cardiac and vascular growth process To test this hypothesis, we examined the presence of polymorphisms within the coding region of the ATI gene using polymerase chain reaction (PCR) and subsequent non- radioactive sequencing of samples from a control group with no previou s history of cardiovascular complaint in individuals or immediate fami ly. Using the Taq-sequencing procedure we found polymorphic sites, esp ecially in the 5' region of the gene (base pair positions 9, 16, 87, 1 33, 186), two of which led to an exchange of the amino acid (amino aci d 6: Ser <-> Pro, amino acid 45: Gly <-> Arg). Together with the silen t polymorphism at base pair position 573, which our group established previously an additional polymorphism in tire 3' region of the gene wa s discovered. This, however, did not confer any changes in amino acid sequence. In a preliminary study we found no association between the d istribution of the C/T-573 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 th e polymorphisms described are associated with cardiovascular disease.