Chromosome 9p21 variant predicts mortality after coronary artery bypass graft surgery.
BACKGROUND
Recent genome-wide association studies have identified several chromosome 9p21 single nucleotide polymorphisms associated with coronary artery disease and myocardial infarction in nonsurgical populations. We have recently demonstrated an independent association between these 9p21 variants and perioperative myocardial injury after isolated primary coronary artery bypass graft (CABG) surgery. This study investigated the association of a 9p21 variant with mortality in patients after CABG surgery and its prognostic value to improve the EuroSCORE.


RESULTS
In a 2-center, prospective, observational study of 846 white primary CABG surgery patients, we genotyped rs10116277, the 9p21 variant with the strongest association to perioperative myocardial injury in our cohort. To estimate the utility of rs10116277 for predicting all-cause mortality within 5 years after surgery, a Cox proportional hazard model was constructed to estimate the hazard ratios (HR) and 95% confidence intervals (CI) while adjusting for demographics and clinical covariates. The homozygote minor allele of rs10116277 was associated with significantly increased risk of all-cause mortality even after adjusting for other clinical predictors of mortality in a Cox proportional hazards model (HR, 1.7; 95% CI, 1.1-2.7; P=0.026). Addition of rs10116277 to the logistic EuroSCORE also significantly improved model prediction for mortality (HR, 1.82; 95% CI, 1.15-2.88; P=0.01).


CONCLUSIONS
The 9p21 variant rs10116277 is independently associated with all-cause mortality after primary CABG surgery in whites and significantly improves the predictive value of the logistic EuroSCORE. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT00281164.
Muehlschlegel
Jochen D
JD
Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. jmuehlschlegel@partners.org.
Liu
Kuang-Yu
KY
Perry
Tjörvi E
TE
Fox
Amanda A
AA
Collard
Charles D
CD
Shernan
Stanton K
SK
Body
Simon C
SC
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics*; D001026:Coronary Artery Bypass; D003324:Coronary Artery Disease / Q000235:genetics / Q000401:mortality; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007431:Intraoperative Complications / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000235:genetics / Q000401:mortality; D020641:Polymorphism, Single Nucleotide; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D011446:Prospective Studies; D015996:Survival Rate; D013997:Time Factors