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


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.


CONCLUSIONS
In this large observational study, the 9p21 variant was independently associated with adverse cardiac outcome after ACS.
Buysschaert
Ian
I
Vesalius Research Center, VIB and KULeuven, Campus Gasthuisberg, Herestraat 49, Box 912, B-3000 Leuven, Belgium.
Carruthers
Kathryn F
KF
Dunbar
Donald R
DR
Peuteman
Gilian
G
Rietzschel
Ernst
E
Belmans
Ann
A
Hedley
Ann
A
De Meyer
Tim
T
Budaj
Andrzej
A
Van de Werf
Frans
F
Lambrechts
Diether
D
Fox
Keith A A
KA
D054058:Acute Coronary Syndrome / Q000235:genetics*; D000368:Aged; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics*; D016757:Death, Sudden, Cardiac / Q000209:etiology*; D005260:Female; D019942:Genes, p16; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005820:Genetic Testing; D005838:Genotype; D006760:Hospitalization; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011446:Prospective Studies; D012008:Recurrence; D012042:Registries; D012307:Risk Factors