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: 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
• Journal: Atherosclerosis (Atherosclerosis) Vol. 201 Issue 1 Pg. 148-54 (Nov 2008) ISSN: 1879-1484 [Electronic] Ireland
• PMID: 18374923 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• 5-Lipoxygenase-Activating Proteins
• ALOX5AP protein, human
• Carrier Proteins
• Membrane Proteins

Topics

• 5-Lipoxygenase-Activating Proteins
• Aged
• Angioplasty, Balloon, Coronary (adverse effects)
• Carrier Proteins (genetics)
• Case-Control Studies
• Cohort Studies
• Coronary Artery Disease (genetics, therapy)
• Coronary Restenosis (genetics)
• Drug-Eluting Stents (adverse effects)
• Female
• Genetic Association Studies
• Graft Occlusion, Vascular (genetics)
• Haplotypes
• Humans
• Male
• Membrane Proteins (genetics)
• Middle Aged
• Polymorphism, Single Nucleotide
• Risk Factors