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

JS Wijpkema, PL van Haelst, PS Monraats, M Bruinenberg, AH Zwinderman, F Zijlstra, G van der Steege, RJ de Winter, PAFM Doevendans, J Waltenberger, JW Jukema, RA Tio*

*Corresponding author voor dit werk

    Onderzoeksoutput: ArticleAcademicpeer review

    30 Citaten (Scopus)

    Samenvatting

    Objectives 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 T81OA, 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.

    Conclusion 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. Pharmacogenetics and Genomics 16:331-337 (c) 2006 Lippincott Williams & Wilkins.

    Originele taal-2English
    Pagina's (van-tot)331-337
    Aantal pagina's7
    TijdschriftPHARMACOGENETICS AND GENOMICS
    Volume16
    Nummer van het tijdschrift5
    StatusPublished - mei-2006

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