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

Svati H. Shah, Elizabeth R. Hauser, David Crosslin, Liyong Wang, Carol Haynes, Jessica Connelly, Sarah Nelson, Jessica Johnson, Shera Gadson, Charlotte L. Nelson, David Seo, Simon Gregory, William E. Kraus, Christopher B. Granger, Pascal Goldschmidt-Clermont, L. Kristin Newby

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

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. Single-nucleotide polymorphisms (SNPs, N = 82) from 39 candidate atherosclerosis genes were genotyped. Multivariable logistic regression models were used to test for association. Results: Five SNPs 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.

Original languageEnglish (US)
Pages (from-to)148-154
Number of pages7
JournalAtherosclerosis
Volume201
Issue number1
DOIs
StatePublished - Nov 2008

Keywords

  • Coronary artery disease
  • Genetics
  • Inflammation
  • Stent restenosis

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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    Shah, S. H., Hauser, E. R., Crosslin, D., Wang, L., Haynes, C., Connelly, J., Nelson, S., Johnson, J., Gadson, S., Nelson, C. L., Seo, D., Gregory, S., Kraus, W. E., Granger, C. B., Goldschmidt-Clermont, P., & Newby, L. K. (2008). ALOX5AP variants are associated with in-stent restenosis after percutaneous coronary intervention. Atherosclerosis, 201(1), 148-154. https://doi.org/10.1016/j.atherosclerosis.2008.01.011