A common variant at chromosome 9P21.3 is associated with age of onset of coronary disease but not subsequent mortality.
BACKGROUND
Chromosome 9p21.3 (chr9p21.3) recently was identified by several genome-wide association studies as the genomic region most strongly associated with the risk of coronary artery disease. Within the chr9p21.3 locus, the single-nucleotide polymorphism rs1333049 has been demonstrated to be most strongly associated with susceptibility to developing coronary artery disease. However, the effect of rs1333049 on clinical outcomes in patients with established coronary disease has yet to be determined.


RESULTS
Coronary Disease Cohort Study (CDCS) (n=1054) and Post-Myocardial Infarction (PMI) (n=816) study participants were genotyped for rs1333049. Clinical history, circulating lipids, neurohormones, cardiac function, and discharge medications were documented. All-cause mortality and cardiovascular hospital readmissions were recorded over a median follow-up period of 4.0 years for the CDCS cohort and 9.1 years for the PMI cohort. The CDCS patients homozygous for the high-risk C allele had an age of onset 2 to 5 years earlier for coronary disease (P=.005), angina (P=.025), myocardial infarction (P=.022), and percutaneous transluminal coronary angioplasty (P=.009). Patients with the CC genotype also had higher levels of total cholesterol (P=.033) and triglycerides (P=.003). The PMI participants with the CC genotype were 3 years younger on admission (P=.009). Cox proportional hazards analysis adjusting for established predictors of increased risk showed no significant association between rs1333049 genotype and mortality in either the CDCS (P=.214) or the PMI (P=.696) cohorts.


CONCLUSIONS
The chr9p21.3 polymorphism rs1333049 was associated with an earlier age of disease onset in 2 coronary disease cohorts but not with poorer clinical outcome in either cohort.
Ellis
Katrina L
KL
Christchurch Cardioendocrine Research Group, Department of Medicine, University of Otago-Christchurch, Christchurch, New Zealand. katrina.ellis@otago.ac.nz
Pilbrow
Anna P
AP
Frampton
Chris M
CM
Doughty
Rob N
RN
Whalley
Gillian A
GA
Ellis
Chris J
CJ
Palmer
Barry R
BR
Skelton
Lorraine
L
Yandle
Tim G
TG
Palmer
Suetonia C
SC
Troughton
Richard W
RW
Richards
A Mark
AM
Cameron
Vicky A
VA
D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D002784:Cholesterol / Q000097:blood; D002899:Chromosomes, Human, Pair 9; D015331:Cohort Studies; D003327:Coronary Disease / Q000453:epidemiology / Q000235:genetics* / Q000401:mortality; D005260:Female; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000235:genetics / Q000401:mortality; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D014280:Triglycerides / Q000097:blood
D014280:Triglycerides; D002784:Cholesterol