title: Interactions between angiotensin-I converting enzyme insertion/deletion polymorphism and response of plasma lipids and coronary atherosclerosis to treatment with fluvastatin: the lipoprotein and coronary atherosclerosis study.
abstract: OBJECTIVE
  Our objectives were to determine whether angiotensin-1 converting enzyme (ACE) insertion/deletion (I/D) polymorphism was associated with the severity of coronary artery disease (CAD) and its progression/regression in response to fluvastatin therapy in the Lipoprotein and Coronary Atherosclerosis Study (LCAS) population.
  
  
  BACKGROUND
  Genetic factors are involved in susceptibility to CAD. Angiotensin-1 converting enzyme I/D polymorphism, which accounts for half of the variance of plasma and tissue levels of ACE, has been implicated in susceptibility to CAD and myocardial infarction (MI).
  
  
  METHODS
  Angiotensin-1 converting enzyme genotypes were determined by polymerase chain reaction (PCR). Fasting plasma lipids were measured and quantitative coronary angiograms were obtained at baseline and 2.5 years following randomization to fluvastatin or placebo.
  
  
  RESULTS
  Ninety-one subjects had DD, 198 ID and 75 II genotypes. The mean blood pressure, minimum lumen diameter (MLD), number of coronary lesions and total occlusions were not significantly different at baseline or follow-up among the genotypes. There was a significant genotype-by-treatment interaction for total cholesterol (p = 0.018), low-density lipoprotein cholesterol (LDL-C) (p = 0.005) and apolipoprotein (apo) B (p = 0.045). In response to fluvastatin therapy, subjects with DD, compared with those with ID and II genotypes, had a greater reduction in total cholesterol (19% vs. 15% vs. 13%), LDL-C (31% vs. 25% vs. 21%) and apo B (23% vs. 15% vs. 12%). Definite progression was less (14%) and regression was more common (24%) in DD as compared with those with ID (32% and 17%) and II (33% and 3%) genotypes (p = 0.023). Changes in the mean MLD and lesion-specific MLD also followed the same trend.
  
  
  CONCLUSIONS
  Angiotensin-1 converting enzyme I/D polymorphism is associated with the response of plasma lipids and coronary atherosclerosis to treatment with fluvastatin. Subjects with DD genotype had a greater reduction in LDL-C, a higher rate of regression and a lower rate of progression of CAD.
authors.affiliation: Department of Medicine, Baylor College of Medicine, Houston, Texas, USA. amarian@bcm.tmc.edu
authors.forename: A J
authors.initials: AJ
authors.lastname: Marian
authors.forename: F
authors.initials: F
authors.lastname: Safavi
authors.forename: L
authors.initials: L
authors.lastname: Ferlic
authors.forename: J K
authors.initials: JK
authors.lastname: Dunn
authors.forename: A M
authors.initials: AM
authors.lastname: Gotto
authors.forename: C M
authors.initials: CM
authors.lastname: Ballantyne
mesh_terms: D000328:Adult; D000368:Aged; D008078:Cholesterol, LDL / Q000097:blood; D002869:Chromosome Aberrations / Q000235:genetics*; D002872:Chromosome Deletion; D003324:Coronary Artery Disease / Q000097:blood / Q000188:drug therapy / Q000235:genetics*; D018450:Disease Progression; D005229:Fatty Acids, Monounsaturated / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D000077340:Fluvastatin; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D007211:Indoles / Q000009:adverse effects / Q000627:therapeutic use*; D008055:Lipids / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000188:drug therapy / Q000235:genetics; D007703:Peptidyl-Dipeptidase A / Q000235:genetics* / Q000502:physiology; D011110:Polymorphism, Genetic / Q000235:genetics*; D016896:Treatment Outcome
chemical_list: D008078:Cholesterol, LDL; D005229:Fatty Acids, Monounsaturated; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007211:Indoles; D008055:Lipids; D000077340:Fluvastatin; D007703:Peptidyl-Dipeptidase A