A study of the relationships between angiotensin- converting enzyme gene, chymase gene polymorphisms, pharmacological treatment with ACE inhibitor and regression of left ventricular hypertrophy in essential hypertension patients treated with benazepril

Ann Hum Biol. 2005 Jan-Feb;32(1):30-43. doi: 10.1080/03014460400027458.

Abstract

Background: About 15-37% of the adult population worldwide suffers from hypertension. Hypertension is responsible for one-third of all global deaths. Left ventricular hypertrophy (LVH) is one of the most important characteristics of hypertension target organ damage and is also an independent risk factor for cardiovascular events. Therefore, effective regression of LVH is a main aim of hypertension treatment and also an important public health concern. However, few studies of the regression of LVH have been reported. In particular, little is known about the relationship between the genotypes of angiotensin-converting enzyme (ACE) and chymase (CMA) genes, and the effectiveness of antihypertensive drugs in regression of LVH.

Aim: The study investigated whether the insertion/deletion (I/D) polymorphism of ACE gene and the A/B polymorphism of the CMA gene are related to the regression of LVH in essential hypertension patients who were participants in a long-term trial of therapy with benazepril.

Subjects and methods: Data from 157 patients was collected and used in the analysis. The genotypes of ACE and CMA genes were identified by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). Left ventricular mass (LVM) was measured by echocardiography, and left ventricular mass index (LVMI) was calculated.

Results: Blood pressure was markedly reduced and heart rate was unchanged by long-term treatment with benazepril. Regression of LVH was observed. The mean reduction in LVMI was 41.50+/-28.48 g m-2. Reduction of LVM, LVMI and percentage reduction of LVMI were more in the DD group than in the II and ID groups (P<0.05). No significant difference in other indices was found in the different genotype groups of ACE (P>0.05). No significant difference in all indices was found among the different genotype groups of CMA (P>0.05). No interaction was found between the genotypes of ACE and CMA.

Conclusion: Hypertension patients with the DD genotype are more likely to have regression of LVH when treated with benazepril than patients with other genotypes of ACE. No evidence was found to support an association between CMA genotype and regression of LVH in patients or to support the interaction between the two genes in regression of LVH.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use*
  • Benzazepines / therapeutic use*
  • Blood Pressure / drug effects
  • Chymases
  • Female
  • Genotype
  • Humans
  • Hypertension / drug therapy*
  • Hypertension / genetics
  • Hypertension / physiopathology
  • Hypertrophy, Left Ventricular / drug therapy*
  • Male
  • Middle Aged
  • Peptidyl-Dipeptidase A / genetics*
  • Polymerase Chain Reaction
  • Polymorphism, Genetic
  • Polymorphism, Restriction Fragment Length
  • Serine Endopeptidases / genetics*
  • Treatment Outcome

Substances

  • Angiotensin-Converting Enzyme Inhibitors
  • Benzazepines
  • Peptidyl-Dipeptidase A
  • Serine Endopeptidases
  • Chymases
  • benazepril