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 M Seo, Simon Gregory, William E. Kraus, Christopher B. Granger, Pascal Goldschmidt-Clermont, L. Kristin Newby

Research output: Contribution to journalArticle

23 Citations (Scopus)

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
Pages (from-to)148-154
Number of pages7
JournalAtherosclerosis
Volume201
Issue number1
DOIs
StatePublished - Nov 1 2008

Fingerprint

Percutaneous Coronary Intervention
Stents
Drug-Eluting Stents
Single Nucleotide Polymorphism
Atherosclerosis
Haplotypes
Logistic Models
Metals
Genes
Leukotrienes
Coronary Artery Disease
Thrombosis

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 journalArticle

Shah, SH, Hauser, ER, Crosslin, D, Wang, L, Haynes, C, Connelly, J, Nelson, S, Johnson, J, Gadson, S, Nelson, CL, Seo, DM, Gregory, S, Kraus, WE, Granger, CB, Goldschmidt-Clermont, P & Newby, LK 2008, 'ALOX5AP variants are associated with in-stent restenosis after percutaneous coronary intervention', Atherosclerosis, vol. 201, no. 1, pp. 148-154. https://doi.org/10.1016/j.atherosclerosis.2008.01.011
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. / ALOX5AP variants are associated with in-stent restenosis after percutaneous coronary intervention. In: Atherosclerosis. 2008 ; Vol. 201, No. 1. pp. 148-154.
@article{4226b648250048f9ae6ec9e90d3cf1cd,
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.",
keywords = "Coronary artery disease, Genetics, Inflammation, Stent restenosis",
author = "Shah, {Svati H.} and Hauser, {Elizabeth R.} and David Crosslin and Liyong Wang and Carol Haynes and Jessica Connelly and Sarah Nelson and Jessica Johnson and Shera Gadson and Nelson, {Charlotte L.} and Seo, {David M} and Simon Gregory and Kraus, {William E.} and Granger, {Christopher B.} and Pascal Goldschmidt-Clermont and Newby, {L. Kristin}",
year = "2008",
month = "11",
day = "1",
doi = "10.1016/j.atherosclerosis.2008.01.011",
language = "English",
volume = "201",
pages = "148--154",
journal = "Atherosclerosis",
issn = "0021-9150",
publisher = "Elsevier Ireland Ltd",
number = "1",

}

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 -