ACE and AT1R gene polymorphisms independently predicted pretreatment blood pressure, whereas AGT genotype independently predicted the blood pressure response to ACE inhibitor monotherapy.
Cohort (n=125)
Do renin-angiotensin system gene polymorphisms influence blood pressure and the response to ACE inhibition in previously untreated essential hypertensives?
Genetic variations in the renin-angiotensin system, specifically ACE, AT1R, and AGT polymorphisms, influence baseline blood pressure and the individual response to ACE inhibitor therapy in essential hypertension.
Objectives To investigate the relationship between polymorphisms in the angiotensin converting enzyme (ACE), angiotensinogen (AGT) and type 1 angiotensin-II (AT1R) genes and (1) quantitative variations in blood 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 hypertensives. Genotypes for ACE insertion and deletion, AGT M235T and AT1R A1166±C polymorphisms were determined in DNA extracted from peripheral blood leucocytes. The influence of genotype on pretreatment blood pressure and the ACE inhibitor-induced decrease in blood pressure was tested by analysis of variance and multiple regression analysis, adjusting for age, sex, body mass index, alcohol intake and, where appropriate, pretreatment blood pressure. Results ACE and AT1R genotypes were independent predictors of pretreatment systolic and diastolic blood pressure, with an apparent interaction between these two gene loci. Although it did not influence pretreatment blood pressure in this population, AGT genotype was an independent predictor of the blood pressure response to ACE inhibition. Conclusions The ACE and AT1R gene loci (chromosomes 17q and 3q, respectively) may carry alleles influencing blood pressure variation in this hypertensive population, with a possible 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 contribute to individual differences in the blood pressure response to ACE inhibition. Among essential hypertensives, differences in the ACE inhibitor response appear, in part, to be genetically determined.
Hingorani et al. (Fri,) conducted a cohort in Essential hypertension (n=125). ACE inhibitors was evaluated on Pretreatment blood pressure and blood pressure response to ACE inhibition. ACE and AT1R gene polymorphisms independently predicted pretreatment blood pressure, whereas AGT genotype independently predicted the blood pressure response to ACE inhibitor monotherapy.