Cited 25 times since 2006 (1.4 per year) source: EuropePMC Pharmacogenetics and genomics, Volume 16, Issue 5, 1 1 2006, Pages 331-337 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. Wijpkema JS, van Haelst PL, Monraats PS, Bruinenberg M, Zwinderman AH, Zijlstra F, van der Steege G, de Winter RJ, Doevendans PA, Waltenberger J, Jukema JW, Tio RA
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 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.
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.
