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Gene dosage of the common variant 9p21 predicts severity of coronary artery disease.

https://arctichealth.org/en/permalink/ahliterature141832
Source
J Am Coll Cardiol. 2010 Aug 3;56(6):479-86
Publication Type
Article
Date
Aug-3-2010
Author
Sonny Dandona
Alexandre F R Stewart
Li Chen
Kathryn Williams
Derek So
Ed O'Brien
Christopher Glover
Michel Lemay
Olivia Assogba
Lan Vo
Yan Qing Wang
Marino Labinaz
George A Wells
Ruth McPherson
Robert Roberts
Author Affiliation
John and Jennifer Ruddy Canadian Cardiovascular Genetics Centre, University of Ottawa Heart Institute, 40 Ruskin Street, Ottawa, Ontario, Canada.
Source
J Am Coll Cardiol. 2010 Aug 3;56(6):479-86
Date
Aug-3-2010
Language
English
Publication Type
Article
Keywords
Age Factors
Age of Onset
Aged
Chromosomes, Human, Pair 9 - genetics
Coronary Angiography
Coronary Artery Disease - epidemiology - genetics - radiography
Cross-Sectional Studies
Electrocardiography
Female
Follow-Up Studies
Gene Dosage
Genetic Predisposition to Disease - epidemiology
Genetic Variation
Genotype
Humans
Male
Middle Aged
Ontario - epidemiology
Prevalence
Retrospective Studies
Risk Assessment - methods
Risk factors
Severity of Illness Index
Abstract
The purpose of this study was to test the hypothesis that 9p21 gene dosage determines the severity of coronary artery disease (CAD).
The 9p21 locus is the first common genetic variant to associate with risk of CAD and/or myocardial infarction in multiple studies.
A cross-sectional study examined nondiabetic patients with CAD defined by coronary angiography to have at least 1 epicardial stenosis >50%. In all, 950 patients with early onset CAD (age 56.1 +/- 9.6 years) and an independent sample of 764 patients with late onset CAD (age 70.0 +/- 8.0 years) were enrolled from the cardiac catheterization laboratories at the University of Ottawa Heart Institute from April 15, 2006, to August 15, 2008, and genotyped for the single nucleotide polymorphism rs1333049 9p21 risk variant. Angiographers were blinded to genotype. The association between 9p21 risk genotype and the proportion of patients with 3-vessel disease, 1-vessel disease, left main trunk disease, and coronary artery bypass graft surgery was tested, as was its association with the modified Gensini and Duke coronary scoring indexes.
Among younger CAD cases, 3-vessel disease demonstrated a strong, direct association with 9p21 gene dosage (p = 4.26 x 10(-4)). Conversely, 1-vessel disease demonstrated a strong inverse association with increasing gene dosage (p = 2.41 x 10(-5)). In the replication sample, gene dosage also predicted 3-vessel disease (p = 6.51 x 10(-6)). Left main trunk disease and coronary artery bypass graft surgery demonstrated a direct strong association with gene dosage (p = 3.66 x 10(-4)) and (p = 2.42 x 10(-2)), respectively. Gene dosage demonstrated a strong, direct association with both the modified Gensini (p
Notes
Comment In: J Am Coll Cardiol. 2011 Mar 29;57(13):1497-8; author reply 1498-921435522
Comment In: J Am Coll Cardiol. 2010 Aug 3;56(6):487-920670759
PubMed ID
20670758 View in PubMed
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