Gene Dosage of the Common Variant 9p21 Predicts Severity of Coronary Artery Disease

Dandona, Sonny; Stewart, Alexandre F.R.; Chen, Li; Williams, Kathryn; So, Derek; O'Brien, Edward R.; Glover, Christopher; Lemay, Michel; Assogba, Olivia; Vo, Lan; Wang, Yan Qing; Labinaz, Marino; Wells, George; McPherson, Ruth; Roberts, Robert

doi:10.1016/j.jacc.2009.10.092

Cited by 136 publications

(137 citation statements)

References 24 publications

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“…While the molecular mechanism of 9p21 is unknown, its site of action has been confirmed. All studies have consistently shown the 9p21 risk variant relates to coronary atherosclerosis and only secondarily to myocardial infarction (32), (33), (34), (35). Some studies have also suggested 9p21 to be associated with the rate of progression of coronary atherosclerosis(32), (35).…”

Section: Discovery Of 9p21 the First Genetic Risk Variant Associatedmentioning

confidence: 99%

A genetic basis for coronary artery disease

Roberts¹

2015

Trends in Cardiovascular Medicine

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Section: Discovery Of 9p21 the First Genetic Risk Variant Associatedmentioning

confidence: 99%

A genetic basis for coronary artery disease

Roberts¹

2015

Trends in Cardiovascular Medicine

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“…The fact that 23 of the 36 risk variables for CHD do not act through any of the known risk factors indicates unknown mechanisms that need to be elucidated. 33 In another review of 35 common variables that affect CHD, the risk for disease did not exceed 13% of the total heritability of CHD. 34 All these findings suggest that there are still many things to be discovered.…”

Section: Genome-wide Association Studymentioning

confidence: 97%

Genetic Association with Coronary Artery Disease

Rahman

Islam

2017

Cardiovasc. j.

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“…A similar analysis with coronary angiography was also performed with 517 patients with late-onset CAD. Approximately 50% of the patients had myocardial infarction superimposed on the atherosclerosis (46 ). The analysis of the 9p21 variant as a risk factor indicated a strong association with coronary atherosclerosis, and 9p21 was a predictor of severity, as assessed by the number of vessels involved (46 ).…”

Section: The Site Of Action For the 9p21 Variant Is The Vessel Wallmentioning

confidence: 98%

“…Approximately 50% of the patients had myocardial infarction superimposed on the atherosclerosis (46 ). The analysis of the 9p21 variant as a risk factor indicated a strong association with coronary atherosclerosis, and 9p21 was a predictor of severity, as assessed by the number of vessels involved (46 ). Individuals with single-vessel disease had the lowest dose of 9p21 risk, whereas individuals with 3-vessel disease had the highest frequency of 2 copies of the 9p21 risk allele.…”

Section: The Site Of Action For the 9p21 Variant Is The Vessel Wallmentioning

confidence: 99%

9p21 and the Genetic Revolution for Coronary Artery Disease

Roberts

Stewart

2012

Clinical Chemistry

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BACKGROUND It has long been recognized that 50% of the susceptibility for coronary artery disease (CAD) is due to predisposing genetic factors. Comprehensive prevention is likely to require knowledge of these genetic factors. CONTENT Using a genomewide association study (GWAS), the Ottawa Heart Genomic Study and the deCODE group simultaneously identified the first genetic risk variant, at chromosome 9p21. The 9p21 variant became the first risk factor to be identified since 1964. 9p21 occurs in 75% of the population except for African Americans and is associated with a 25% increased risk for CAD with 1 copy and a 50% increased risk with 2 copies. Perhaps the most remarkable finding is that 9p21 is independent of all known risk factors, indicating there are factors contributing to the pathogenesis of CAD that are yet unknown. 9p21 in individuals with premature CAD is associated with a 2-fold increase in risk, similar to that of smoking and cholesterol. Routine genetic testing will probably remain controversial until a specific treatment is developed. Over a period of 5 years, however, GWASs have identified 30 genetic variants for CAD risk, of which only 6 act through the known risk factors. SUMMARY The 9p21 variant has now been established as an independent risk factor for CAD and, along with the additional 29 risk genetic variants recently identified, is likely to provide the thrust for genetic testing and personalized medicine in the near future.

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Gene Dosage of the Common Variant 9p21 Predicts Severity of Coronary Artery Disease

Abstract: Gene dosage of the common risk variant 9p21 predicts the severity of coronary atheromatous burden.

Cited by 136 publications

References 24 publications

A genetic basis for coronary artery disease

A genetic basis for coronary artery disease

Genetic Association with Coronary Artery Disease

9p21 and the Genetic Revolution for Coronary Artery Disease

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