A variant at chromosome 9p21 is associated with recurrent myocardial infarction and cardiac death after acute coronary syndrome: the GRACE Genetics Study

UMMS Affiliation

Center for Outcomes Research

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Document Type



Acute Coronary Syndrome; Aged; Chromosomes, Human, Pair 9; Death, Sudden, Cardiac; Female; *Genes, p16; Genetic Predisposition to Disease; Genetic Testing; Genotype; Hospitalization; Humans; Male; Middle Aged; Myocardial Infarction; Polymorphism, Single Nucleotide; Prospective Studies; Recurrence; Registries; Risk Factors


Cardiovascular System | Cells | Genetic Phenomena | Genetics | Health Services Research | Investigative Techniques | Pathological Conditions, Signs and Symptoms


AIMS: Recent genetic studies identified the rs1333049 variant on chromosome 9p21 as a major susceptibility locus for coronary artery disease and myocardial infarction (MI). Here, we evaluated whether this variant also contributes to recurrent MI or cardiac death following an acute coronary syndrome (ACS).

METHODS AND RESULTS: A total of 3247 patients with ACS enrolled in the Global Registry of Acute Coronary Events (GRACE) in three distinct populations (UK, Belgium and Poland) were prospectively followed for 6 months and genotyped for rs1333049, in addition to 3004 and 2467 healthy controls from the UK and Belgium. After having confirmed that the at-risk C allele of rs1333049 was associated with index ACS in the UK and Belgian populations, we found that the rs1333049 at-risk C allele was significantly and independently associated with recurrent MI [age- and gender-adjusted hazard ratio (HR) 1.48, CI = 1.00-2.19, P = 0.048; and multivariable-adjusted HR 1.47, CI = 0.99-2.18; P = 0.053] and with recurrent MI or cardiac death (age- and gender-adjusted HR 1.58, CI = 1.00-2.48; P = 0.045; and multivariable adjusted HR 1.49, CI = 1.03-1.98; P = 0.028) within 6 months after an index ACS. Inclusion of rs1333049 into the GRACE risk score significantly improved classification for recurrent MI or cardiac death (P = 0.040), as calculated by the integrated discrimination improvement method.

CONCLUSION: In this large observational study, the 9p21 variant was independently associated with adverse cardiac outcome after ACS.


Chromosome 9p21, Rs1333049, Genetics, Acute coronary syndrome, Myocardial infarction, Plaque rupture

DOI of Published Version



Eur Heart J. 2010 May;31(9):1132-41. Epub 2010 Mar 15. Link to article on publisher's site

Journal/Book/Conference Title

European heart journal

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