Variation in the 4q25 chromosomal locus predicts atrial fibrillation after coronary artery bypass graft surgery.
BACKGROUND
Atrial fibrillation (AF) is the most common adverse event following coronary artery bypass graft surgery. A recent study identified chromosome 4q25 variants associated with AF in ambulatory populations. However, their role in postoperative AF is unknown. We hypothesized that genetic variants in the 4q25 chromosomal region are independently associated with postoperative AF after coronary artery bypass graft surgery.


RESULTS
Two prospectively collected cohorts of patients undergoing coronary artery bypass graft surgery, with or without concurrent valve surgery, at 3 US centers. From a discovery cohort of 959 patients, clinical and genomic multivariate predictors of postoperative AF were identified by genotyping 45 single-nucleotide polymorphisms (SNPs) encompassing the 4q25 locus. Three SNPs were then assessed in a separately collected validation cohort of 494 patients. After adjustment for clinical predictors of postoperative AF and multiple comparisons, rs2200733, rs13143308, and 5 other linked SNPs independently predicted postoperative AF in the discovery cohort. Additive odds ratios for the 7 associated 4q25 SNPs ranged between 1.57 and 2.17 (P=8.0x10(-4) to 3.4x10(-6)). Association with postoperative AF were measured and replicated for rs2200733 and rs13143308 in the validation cohort.


CONCLUSIONS
In 2 independently collected cardiac surgery cohorts, noncoding SNPs within the chromosome 4q25 region are independently associated with postoperative AF after coronary artery bypass graft surgery after adjusting for clinical covariates and multiple comparisons.
Body
Simon C
SC
Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass 02115, USA. body@zeus.bwh.harvard.edu
Collard
Charles D
CD
Shernan
Stanton K
SK
Fox
Amanda A
AA
Liu
Kuang-Yu
KY
Ritchie
Marylyn D
MD
Perry
Tjörvi E
TE
Muehlschlegel
Jochen D
JD
Aranki
Sary
S
Donahue
Brian S
BS
Pretorius
Mias
M
Estrada
Juan-Carlos
JC
Ellinor
Patrick T
PT
Newton-Cheh
Christopher
C
Seidman
Christine E
CE
Seidman
J G
JG
Herman
Daniel S
DS
Lichtner
Peter
P
Meitinger
Thomas
T
Pfeufer
Arne
A
Kääb
Stefan
S
Brown
Nancy J
NJ
Roden
Dan M
DM
Darbar
Dawood
D
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001281:Atrial Fibrillation / Q000209:etiology / Q000235:genetics*; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics*; D001026:Coronary Artery Bypass / Q000009:adverse effects*; D005260:Female; D014644:Genetic Variation; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011183:Postoperative Complications / Q000209:etiology*; D011237:Predictive Value of Tests; D011446:Prospective Studies; D055815:Young Adult