title: ALOX5AP variants are associated with in-stent restenosis after percutaneous coronary intervention.
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.
authors: Department of Medicine, Duke University Medical Center, Durham, NC 27710, United States. svati.shah@duke.edu
authors: Svati H
authors: SH
authors: Shah
authors: Elizabeth R
authors: ER
authors: Hauser
authors: David
authors: D
authors: Crosslin
authors: Liyong
authors: L
authors: Wang
authors: Carol
authors: C
authors: Haynes
authors: Jessica
authors: J
authors: Connelly
authors: Sarah
authors: S
authors: Nelson
authors: Jessica
authors: J
authors: Johnson
authors: Shera
authors: S
authors: Gadson
authors: Charlotte L
authors: CL
authors: Nelson
authors: David
authors: D
authors: Seo
authors: Simon
authors: S
authors: Gregory
authors: William E
authors: WE
authors: Kraus
authors: Christopher B
authors: CB
authors: Granger
authors: Pascal
authors: P
authors: Goldschmidt-Clermont
authors: L Kristin
authors: LK
authors: Newby
mesh_terms: D058927:5-Lipoxygenase-Activating Proteins; D000368:Aged; D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects*; D002352:Carrier Proteins / Q000235:genetics*; D016022:Case-Control Studies; D015331:Cohort Studies; D003324:Coronary Artery Disease / Q000235:genetics* / Q000628:therapy; D023903:Coronary Restenosis / Q000235:genetics*; D054855:Drug-Eluting Stents / Q000009:adverse effects*; D005260:Female; D056726:Genetic Association Studies; D006083:Graft Occlusion, Vascular / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
chemical_list: D058927:5-Lipoxygenase-Activating Proteins; C548592:ALOX5AP protein, human; D002352:Carrier Proteins; D008565:Membrane Proteins