ALOX5AP variants are associated with in-stent restenosis after percutaneous coronary intervention

Background: Use of drug-eluting stents (DES) has reduced in-stent restenosis after percutaneous coronary intervention (PCI); however, DES are associated with late stent thrombosis. There is no accurate way to predict in-stent restenosis, although risk factors for atherosclerosis overlap those for in-stent restenosis. Therefore. we evaluated atherosclerosis candidate genes for association with in-stent restenosis. Methods: We identified 46 consecutive cases that had undergone PCI with bare-metal stents who subsequently developed symptomatic in-stent restenosis of the target lesion (>= 75% luminal narrowing) within 6 months. Forty-six age-, race-, vessel-diameter- and sex-matched controls without in-stent restenosis after PCI with bare-metal stent were also identified. Sin-le-nucleotide polymorphisms (SNPs. N=82) from 39 candidate atherosclerosis genes were genotyped. Multivariable logistic regression models were used to test for association. Results: Five SNP were associated with in-stent restenosis. Three ALOX5AP SNPs were most strongly associated. two with increased risk (OR 3.74, p = 0.01; OR 3.46, p = 0.02), and the third with decreased risk of in-stent restenosis (OR 0.09, p = 0.004). Two ALOX5AP haplotypes were associated with in-stent restenosis (HapB: OR 3.13, p = 0.03) and a haplotype similar to HapA: OR 0.14, p = 0.0009). Conclusions: ALOX5AP, a gene within the inflammatory leukotriene pathway linked to and associated with coronary atherosclerosis, is also associated with in-stent restenosis. Genotyping these variants may help identify those at risk for in-stent restenosis who Would benefit most from use of DES. (C) 2008 Elsevier Ireland Ltd. All rights reserved.