Document Detail


Variation in the 4q25 chromosomal locus predicts atrial fibrillation after coronary artery bypass graft surgery.
MedLine Citation:
PMID:  20031626     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
METHODS AND 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.
Authors:
Simon C Body; Charles D Collard; Stanton K Shernan; Amanda A Fox; Kuang-Yu Liu; Marylyn D Ritchie; Tjörvi E Perry; Jochen D Muehlschlegel; Sary Aranki; Brian S Donahue; Mias Pretorius; Juan-Carlos Estrada; Patrick T Ellinor; Christopher Newton-Cheh; Christine E Seidman; J G Seidman; Daniel S Herman; Peter Lichtner; Thomas Meitinger; Arne Pfeufer; Stefan Kääb; Nancy J Brown; Dan M Roden; Dawood Darbar
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Publication Detail:
Type:  Clinical Trial; Journal Article; Research Support, N.I.H., Extramural     Date:  2009-08-02
Journal Detail:
Title:  Circulation. Cardiovascular genetics     Volume:  2     ISSN:  1942-3268     ISO Abbreviation:  Circ Cardiovasc Genet     Publication Date:  2009 Oct 
Date Detail:
Created Date:  2009-12-24     Completed Date:  2010-03-23     Revised Date:  2014-09-24    
Medline Journal Info:
Nlm Unique ID:  101489144     Medline TA:  Circ Cardiovasc Genet     Country:  United States    
Other Details:
Languages:  eng     Pagination:  499-506     Citation Subset:  IM    
Data Bank Information
Bank Name/Acc. No.:
ClinicalTrials.gov/NCT00281164
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Aged, 80 and over
Atrial Fibrillation / etiology,  genetics*
Chromosomes, Human, Pair 4 / genetics*
Coronary Artery Bypass / adverse effects*
Female
Genetic Variation*
Humans
Male
Middle Aged
Polymorphism, Single Nucleotide
Postoperative Complications / etiology*
Predictive Value of Tests
Prospective Studies
Young Adult
Grant Support
ID/Acronym/Agency:
HL068774/HL/NHLBI NIH HHS; HL092217/HL/NHLBI NIH HHS; HL65962/HL/NHLBI NIH HHS; K23 HL068774/HL/NHLBI NIH HHS; K23 HL068774-01A1/HL/NHLBI NIH HHS; K23 HL068774-02/HL/NHLBI NIH HHS; K23 HL068774-03/HL/NHLBI NIH HHS; K23 HL068774-04/HL/NHLBI NIH HHS; K23 HL068774-05/HL/NHLBI NIH HHS; R01 HL084553/HL/NHLBI NIH HHS; R01 HL092217/HL/NHLBI NIH HHS; R01 HL092217-01A2/HL/NHLBI NIH HHS; R01 HL104156/HL/NHLBI NIH HHS; R21 DA027021/DA/NIDA NIH HHS; T32 GM007753/GM/NIGMS NIH HHS; U01 HL065962/HL/NHLBI NIH HHS; U01 HL065962-09/HL/NHLBI NIH HHS
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