RENIN-ANGIOTENSIN SYSTEM GENE POLYMORPHISMS INFLUENCE BLOOD-PRESSURE AND THE RESPONSE TO ANGIOTENSIN-CONVERTING ENZYME-INHIBITION

Objectives: To investigate the relationship between polymorphisms in t he angiotensin converting enzyme (ACE), angiotensinogen (AGT) and type 1 angiotensin-ll (AT(1)R) genes and (1) quantitative variations in bl ood pressure and (2) the blood pressure response to ACE inhibition in a hypertensive cohort. Design and methods: We administered monotherapy with ACE inhibitors to 125 previously untreated essential hypertensiv es. Genotypes for ACE insertion and deletion, AGT M235T and AT(1)R A(1 166)-->C polymorphisms were determined in DNA extracted from periphera l blood leucocytes. The influence of genotype on pretreatment blood pr essure and the ACE inhibitor-induced decrease in blood pressure was te sted by analysis of variance and multiple regression analysis, adjusti ng for age, sex, body mass index, alcohol intake and, where appropriat e, pretreatment blood pressure. Results: ACE and AT(1)R genotypes were independent predictors of pretreatment systolic and diastolic blood p ressure, with an apparent interaction between these two gene loci. Alt hough it did not influence pretreatment blood pressure in this populat ion, AGT genotype was an independent predictor of the blood pressure r esponse to ACE inhibition. Conclusions: The ACE and AT(1)R gene loci ( chromosomes 17q and 3q, respectively) may carry alleles influencing bl ood pressure variation in this hypertensive population, with a possibl e epistatic interaction between the two loci. The AGT T235 allele does not appear to be a marker for blood pressure variation in this group, but variants on chromosome 1q lying in or near the AGT gene may contr ibute to individual differences in the blood pressure response to ACE inhibition. Among essential hypertensives, differences in the ACE inhi bitor response appear, in part, to be genetically determined.