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 language | English |
|---|---|
| Pages (from-to) | 148-154 |
| Number of pages | 7 |
| Journal | Atherosclerosis |
| Volume | 201 |
| Issue number | 1 |
| DOIs | |
| State | Published - Nov 1 2008 |
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Keywords
- Coronary artery disease
- Genetics
- Inflammation
- Stent restenosis
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine
Cite this
ALOX5AP variants are associated with in-stent restenosis after percutaneous coronary intervention. / Shah, Svati H.; Hauser, Elizabeth R.; Crosslin, David; Wang, Liyong; Haynes, Carol; Connelly, Jessica; Nelson, Sarah; Johnson, Jessica; Gadson, Shera; Nelson, Charlotte L.; Seo, David M; Gregory, Simon; Kraus, William E.; Granger, Christopher B.; Goldschmidt-Clermont, Pascal; Newby, L. Kristin.
In: Atherosclerosis, Vol. 201, No. 1, 01.11.2008, p. 148-154.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - ALOX5AP variants are associated with in-stent restenosis after percutaneous coronary intervention
AU - Shah, Svati H.
AU - Hauser, Elizabeth R.
AU - Crosslin, David
AU - Wang, Liyong
AU - Haynes, Carol
AU - Connelly, Jessica
AU - Nelson, Sarah
AU - Johnson, Jessica
AU - Gadson, Shera
AU - Nelson, Charlotte L.
AU - Seo, David M
AU - Gregory, Simon
AU - Kraus, William E.
AU - Granger, Christopher B.
AU - Goldschmidt-Clermont, Pascal
AU - Newby, L. Kristin
PY - 2008/11/1
Y1 - 2008/11/1
N2 - 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.
AB - 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.
KW - Coronary artery disease
KW - Genetics
KW - Inflammation
KW - Stent restenosis
UR - http://www.scopus.com/inward/record.url?scp=53849085513&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=53849085513&partnerID=8YFLogxK
U2 - 10.1016/j.atherosclerosis.2008.01.011
DO - 10.1016/j.atherosclerosis.2008.01.011
M3 - Article
C2 - 18374923
AN - SCOPUS:53849085513
VL - 201
SP - 148
EP - 154
JO - Atherosclerosis
JF - Atherosclerosis
SN - 0021-9150
IS - 1
ER -