title: Restenosis after percutaneous coronary intervention is associated with the angiotensin-II type-1 receptor 1166A/C polymorphism but not with polymorphisms of angiotensin-converting enzyme, angiotensin-II receptor, angiotensinogen or heme oxygenase-1.
abstract: OBJECTIVE
  The renin-angiotensin system (RAS) is thought to play a major role in the pathophysiology of de-novo restenotic lesions and in-stent restenosis after percutaneous coronary intervention (PCI). Heme oxygenase-1 (HO-1), is thought to beneficially influence these processes. We examined the effect of pharmacologic as well as genetic RAS interactions on restenosis in a large population of consecutive patients undergoing PCI, and evaluated possible gene-gene interactions in both systems.
  
  
  METHODS
  The GENDER project is a multicenter prospective follow-up study, including 3146 patients after successful PCI. Genotyping in these patients was performed for the ACE gene insertion/deletion, the angiotensinogen 235Met/Thr, T174M and A(-6)G, the angiotensin-II type 1 receptor (AT1R) 1166A/C and T810A, the angiotensin-II type 2 receptor (AT2R) 1675G/A and 3123A polymorphisms and the length polymorphism in the HO-1 promoter region.
  
  
  RESULTS
  A total of 3104 patients were followed for 10 months. In 2975 patients at least one of the nine genotypes could be determined. The AT1R 1166 CC genotype showed a significant association with TVR; the other polymorphisms did not. RAS-inhibitory drugs were not associated with the incidence of TVR, nor did they interact with any of the investigated polymorphisms. Patients with the ACE I/I polymorphism showed a trend towards a better outcome if they had a short number of repeats in the HO-1 promoter. This relationship was inversely present in carriers of the ACE D/D polymorphism.
  
  
  CONCLUSIONS
  We could only establish a role for the AT1R 1166A/C polymorphism in restenosis after PCI. However, significant gene-gene interaction was suggested for the ACE gene and the HO-1 promotor. The RAS and HO-1 relation in restenosis merits further investigation.
authors.affiliation: Thoraxcenter, Department of Cardiology, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands.
authors.forename: Jasper S
authors.initials: JS
authors.lastname: Wijpkema
authors.forename: Paul L
authors.initials: PL
authors.lastname: van Haelst
authors.forename: Pascalle S
authors.initials: PS
authors.lastname: Monraats
authors.forename: Marcel
authors.initials: M
authors.lastname: Bruinenberg
authors.forename: Aeilko H
authors.initials: AH
authors.lastname: Zwinderman
authors.forename: Felix
authors.initials: F
authors.lastname: Zijlstra
authors.forename: Gerrit
authors.initials: G
authors.lastname: van der Steege
authors.forename: Rob J
authors.initials: RJ
authors.lastname: de Winter
authors.forename: Pieter A F M
authors.initials: PA
authors.lastname: Doevendans
authors.forename: Johannes
authors.initials: J
authors.lastname: Waltenberger
authors.forename: J Wouter
authors.initials: JW
authors.lastname: Jukema
authors.forename: René A
authors.initials: RA
authors.lastname: Tio
mesh_terms: D000483:Alleles; D015906:Angioplasty, Balloon, Coronary; D000808:Angiotensinogen / Q000235:genetics; D003327:Coronary Disease / Q000235:genetics / Q000628:therapy*; D023903:Coronary Restenosis / Q000235:genetics* / Q000517:prevention & control; D005500:Follow-Up Studies; D051547:Heme Oxygenase-1 / Q000235:genetics; D006801:Humans; D015337:Multicenter Studies as Topic; D007703:Peptidyl-Dipeptidase A / Q000235:genetics; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D011446:Prospective Studies; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics*; D011945:Receptors, Angiotensin / Q000235:genetics; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin; D000808:Angiotensinogen; D051547:Heme Oxygenase-1; D007703:Peptidyl-Dipeptidase A