Insertion/deletion Genotype Research Articles

Relationship between the angiotensin-converting enzyme genotype and the forearm vasodilator response to estrogen replacement therapy in postmenopausal women

OBJECTIVESWe sought to evaluate the relationship between the angiotensin-converting enzyme (ACE) genotype and the change in forearm vasoreactivity in response to a three-month course of oral estrogen in postmenopausal women.BACKGROUNDThe ACE genotype is a known predictor of the response to an ACE inhibitor drug; however, it is not clear whether it can modify the effect of estrogen replacement therapy (ERT) on endothelial function in postmenopausal women.METHODSFifty-five postmenopausal women received 0.625 mg of conjugated equine estrogen daily for three months. Forearm blood flow (FBF) was measured by strain-gauge plethysmography.RESULTSTwenty-one, 25 and 9 patients had the insertion/deletion (ID), II and DD genotypes, respectively. Plasma ACE activity was significantly higher at baseline in patients with either the DD or ID genotype than in those with the II genotype (p < 0.05). A significant decrease in plasma ACE activity with ERT was seen in the ID and II genotypes (p < 0.05), but not in the DD genotype. There were no significant differences in the FBF responses to reactive hyperemia at baseline between the three groups. Estrogen replacement therapy did not alter the FBF response to reactive hyperemia in the DD genotype (4.0 ± 1.3%), although ERT significantly increased the FBF response in the ID and II genotypes (32.6 ± 7.5% and 30.6 ± 6.5%, respectively; p < 0.05). Forearm blood flow after administration of sublingual nitroglycerin did not change over three months in any of the three groups.CONCLUSIONSThese findings suggest that the effect of ERT in postmenopausal women on forearm endothelial function may be determined in part by the genotype of the ACE gene.

Association between angiotensin-converting enzyme gene polymorphisms and regression of left ventricular hypertrophy in patients treated with angiotensin-converting enzyme inhibitors

PURPOSE: An insertion/deletion (ID) polymorphism of the angiotensin-converting enzyme (ACE) gene is associated with left ventricular hypertrophy. The present study examined polymorphisms of the ACE gene in patients with essential hypertension and left ventricular hypertrophy who were participants in a long-term trial of therapy with an ACE inhibitor. PATIENTS AND METHODS: ACE inhibitor therapy was administered for >2 years to 54 patients with hypertension who had moderate or severe left ventricular hypertrophy. Cardiac dimensions were monitored by echocardiography before the initiation of therapy and after 1 and 2 years of treatment. Serum ACE activity and plasma concentrations of brain natriuretic peptide, a marker for left ventricular hypertrophy, were also monitored. RESULTS: Eighteen patients had the II genotype for the angiotensin-converting enzyme gene, 19 had the ID genotype, and 17 had the DD genotype. Baseline (mean ± SD) serum ACE activity was significantly greater ( P <0.05) in the DD (18 ± 7 IU/L) group than in the II (7 ± 4 IU/L) or ID (12 ± 6 IU/L) groups. ACE inhibitor therapy was effective in controlling blood pressure, and it reduced posterior and septal wall thickness, left ventricular mass index, and plasma brain natriuretic peptide concentration in all three groups. Despite similar blood pressure reductions, after 2 years, mean (±SD) regression in posterior wall thickness was significantly less ( P <0.05) in the DD group (−9% ± 5%) than in the ID (−21% ± 7%) and II (−21% ± 9%) groups. Similar results were seen for the reductions in brain natriuretic peptide levels. The magnitudes of regression of septal wall thickness and left ventricular mass index during therapy were less in the DD group than the II group ( P <0.05). CONCLUSION: Hypertensive patients with the DD genotype are less likely to have regression of left ventricular hypertrophy when treated with ACE inhibitors than are patients with other ACE genotypes.