The chromosome 9p21 risk locus is associated with angiographic severity and progression of coronary artery disease

Riyaz S. Patel, Shaoyong Su, Ian J. Neeland, Ayushi Ahuja, Emir Veledar, Jinying Zhao, Anna Helgadottir, Hilma Holm, Jeffrey R. Gulcher, Kari Stefansson, Salina Waddy, Viola Vaccarino, A. Maziar Zafari, Arshed A. Quyyumi

Research output: Contribution to journalArticle

64 Citations (Scopus)

Abstract

Aims We tested the hypothesis that the 9p21 risk locus promotes atherosclerosis by examining the association between rs10757278 and coronary artery disease (CAD) severity and progression determined by semi-quantitative angiographic scores. Methods and results The rs10757278 single nucleotide polymorphism (SNP) was genotyped as the marker for the 9p21 locus in 2334 Caucasian patients undergoing cardiac catheterization (mean age 63, male 67). Angiographic CAD was assessed using two semi-quantitative scoring systems with one estimating severity (Gensini) and the other extent (Sullivan). A subset of 308 patients who underwent two or more coronary angiograms at least 6 months apart were examined for net change in Gensini and Sullivan scores over time to determine the rate of CAD progression by genotype and were further classified as 'progressors' or 'non-progressors' based on absolute change per year in angiographic severity score. We replicated the association between the rs10757278 SNP and myocardial infarction and binary (presence/absence) angiographic classifications of CAD. Furthermore, we observed a significant additive association with this SNP, and both severity and extent of CAD using angiographic scores, after adjustment for age, gender, body mass index, traditional cardiovascular risk factors, myocardial infarction, and statin use (Gensini P = 0.016, Sullivan P = 0.005). In addition, there was a significant linear association with CAD progression before and after adjustment for covariates (Gensini P = 0.023, Sullivan P = 0.003) with homozygotes for the risk variant having three-fold greater odds of CAD progression compared with the referent group. Conclusion The 9p21 risk locus is associated with angiographically defined severity, extent, and progression of CAD, suggesting a role for this locus in influencing atherosclerosis and its progression.

Original languageEnglish (US)
Pages (from-to)3017-3023
Number of pages7
JournalEuropean Heart Journal
Volume31
Issue number24
DOIs
StatePublished - Dec 1 2010
Externally publishedYes

Fingerprint

Coronary Artery Disease
Chromosomes
Disease Progression
Single Nucleotide Polymorphism
Atherosclerosis
Myocardial Infarction
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Homozygote
Cardiac Catheterization
Angiography
Body Mass Index
Genotype

Keywords

  • 9p21
  • Atherosclerosis
  • angiography
  • coronary disease
  • genetics
  • genomics

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

The chromosome 9p21 risk locus is associated with angiographic severity and progression of coronary artery disease. / Patel, Riyaz S.; Su, Shaoyong; Neeland, Ian J.; Ahuja, Ayushi; Veledar, Emir; Zhao, Jinying; Helgadottir, Anna; Holm, Hilma; Gulcher, Jeffrey R.; Stefansson, Kari; Waddy, Salina; Vaccarino, Viola; Zafari, A. Maziar; Quyyumi, Arshed A.

In: European Heart Journal, Vol. 31, No. 24, 01.12.2010, p. 3017-3023.

Research output: Contribution to journalArticle

Patel, RS, Su, S, Neeland, IJ, Ahuja, A, Veledar, E, Zhao, J, Helgadottir, A, Holm, H, Gulcher, JR, Stefansson, K, Waddy, S, Vaccarino, V, Zafari, AM & Quyyumi, AA 2010, 'The chromosome 9p21 risk locus is associated with angiographic severity and progression of coronary artery disease', European Heart Journal, vol. 31, no. 24, pp. 3017-3023. https://doi.org/10.1093/eurheartj/ehq272
Patel, Riyaz S. ; Su, Shaoyong ; Neeland, Ian J. ; Ahuja, Ayushi ; Veledar, Emir ; Zhao, Jinying ; Helgadottir, Anna ; Holm, Hilma ; Gulcher, Jeffrey R. ; Stefansson, Kari ; Waddy, Salina ; Vaccarino, Viola ; Zafari, A. Maziar ; Quyyumi, Arshed A. / The chromosome 9p21 risk locus is associated with angiographic severity and progression of coronary artery disease. In: European Heart Journal. 2010 ; Vol. 31, No. 24. pp. 3017-3023.
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abstract = "Aims We tested the hypothesis that the 9p21 risk locus promotes atherosclerosis by examining the association between rs10757278 and coronary artery disease (CAD) severity and progression determined by semi-quantitative angiographic scores. Methods and results The rs10757278 single nucleotide polymorphism (SNP) was genotyped as the marker for the 9p21 locus in 2334 Caucasian patients undergoing cardiac catheterization (mean age 63, male 67). Angiographic CAD was assessed using two semi-quantitative scoring systems with one estimating severity (Gensini) and the other extent (Sullivan). A subset of 308 patients who underwent two or more coronary angiograms at least 6 months apart were examined for net change in Gensini and Sullivan scores over time to determine the rate of CAD progression by genotype and were further classified as 'progressors' or 'non-progressors' based on absolute change per year in angiographic severity score. We replicated the association between the rs10757278 SNP and myocardial infarction and binary (presence/absence) angiographic classifications of CAD. Furthermore, we observed a significant additive association with this SNP, and both severity and extent of CAD using angiographic scores, after adjustment for age, gender, body mass index, traditional cardiovascular risk factors, myocardial infarction, and statin use (Gensini P = 0.016, Sullivan P = 0.005). In addition, there was a significant linear association with CAD progression before and after adjustment for covariates (Gensini P = 0.023, Sullivan P = 0.003) with homozygotes for the risk variant having three-fold greater odds of CAD progression compared with the referent group. Conclusion The 9p21 risk locus is associated with angiographically defined severity, extent, and progression of CAD, suggesting a role for this locus in influencing atherosclerosis and its progression.",
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T1 - The chromosome 9p21 risk locus is associated with angiographic severity and progression of coronary artery disease

AU - Patel, Riyaz S.

AU - Su, Shaoyong

AU - Neeland, Ian J.

AU - Ahuja, Ayushi

AU - Veledar, Emir

AU - Zhao, Jinying

AU - Helgadottir, Anna

AU - Holm, Hilma

AU - Gulcher, Jeffrey R.

AU - Stefansson, Kari

AU - Waddy, Salina

AU - Vaccarino, Viola

AU - Zafari, A. Maziar

AU - Quyyumi, Arshed A.

PY - 2010/12/1

Y1 - 2010/12/1

N2 - Aims We tested the hypothesis that the 9p21 risk locus promotes atherosclerosis by examining the association between rs10757278 and coronary artery disease (CAD) severity and progression determined by semi-quantitative angiographic scores. Methods and results The rs10757278 single nucleotide polymorphism (SNP) was genotyped as the marker for the 9p21 locus in 2334 Caucasian patients undergoing cardiac catheterization (mean age 63, male 67). Angiographic CAD was assessed using two semi-quantitative scoring systems with one estimating severity (Gensini) and the other extent (Sullivan). A subset of 308 patients who underwent two or more coronary angiograms at least 6 months apart were examined for net change in Gensini and Sullivan scores over time to determine the rate of CAD progression by genotype and were further classified as 'progressors' or 'non-progressors' based on absolute change per year in angiographic severity score. We replicated the association between the rs10757278 SNP and myocardial infarction and binary (presence/absence) angiographic classifications of CAD. Furthermore, we observed a significant additive association with this SNP, and both severity and extent of CAD using angiographic scores, after adjustment for age, gender, body mass index, traditional cardiovascular risk factors, myocardial infarction, and statin use (Gensini P = 0.016, Sullivan P = 0.005). In addition, there was a significant linear association with CAD progression before and after adjustment for covariates (Gensini P = 0.023, Sullivan P = 0.003) with homozygotes for the risk variant having three-fold greater odds of CAD progression compared with the referent group. Conclusion The 9p21 risk locus is associated with angiographically defined severity, extent, and progression of CAD, suggesting a role for this locus in influencing atherosclerosis and its progression.

AB - Aims We tested the hypothesis that the 9p21 risk locus promotes atherosclerosis by examining the association between rs10757278 and coronary artery disease (CAD) severity and progression determined by semi-quantitative angiographic scores. Methods and results The rs10757278 single nucleotide polymorphism (SNP) was genotyped as the marker for the 9p21 locus in 2334 Caucasian patients undergoing cardiac catheterization (mean age 63, male 67). Angiographic CAD was assessed using two semi-quantitative scoring systems with one estimating severity (Gensini) and the other extent (Sullivan). A subset of 308 patients who underwent two or more coronary angiograms at least 6 months apart were examined for net change in Gensini and Sullivan scores over time to determine the rate of CAD progression by genotype and were further classified as 'progressors' or 'non-progressors' based on absolute change per year in angiographic severity score. We replicated the association between the rs10757278 SNP and myocardial infarction and binary (presence/absence) angiographic classifications of CAD. Furthermore, we observed a significant additive association with this SNP, and both severity and extent of CAD using angiographic scores, after adjustment for age, gender, body mass index, traditional cardiovascular risk factors, myocardial infarction, and statin use (Gensini P = 0.016, Sullivan P = 0.005). In addition, there was a significant linear association with CAD progression before and after adjustment for covariates (Gensini P = 0.023, Sullivan P = 0.003) with homozygotes for the risk variant having three-fold greater odds of CAD progression compared with the referent group. Conclusion The 9p21 risk locus is associated with angiographically defined severity, extent, and progression of CAD, suggesting a role for this locus in influencing atherosclerosis and its progression.

KW - 9p21

KW - Atherosclerosis

KW - angiography

KW - coronary disease

KW - genetics

KW - genomics

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