title: Association of the 98T ELAM-1 polymorphism with increased bleeding after cardiac surgery.
abstract: OBJECTIVE
  Hemorrhage continues to be a major problem after cardiac surgery despite the routine use of antifibrinolytic drugs, with striking inter-patient variability poorly explained by already known risk factors. The authors tested the hypothesis that genetic polymorphisms of inflammatory mediators and cellular adhesion molecules are associated with bleeding after cardiac surgery.
  
  
  METHODS
  Prospective, observational study.
  
  
  METHODS
  Single, tertiary referral university heart center.
  
  
  METHODS
  Adult patients undergoing aortocoronary surgery with cardiopulmonary bypass.
  
  
  METHODS
  Patients (n = 759) had 10 mL of blood drawn preoperatively and genomic DNA isolated then genotyped for 17 polymorphisms in 7 candidate genes: tumor necrosis factor, interleukins 1beta and 6, interleukin 1 receptor antagonist, intercellular adhesion molecule-1 (ICAM-1), P-selectin and endothelial leucocyte adhesion molecule-1 (E-selectin). Multivariate analyses were used to relate clinical and genetic factors to bleeding and transfusion.
  
  
  RESULTS
  The 98G/T polymorphism of the E-selectin gene was independently associated with bleeding after cardiac surgery (p = 0.002), after adjusting for significant clinical predictors (patient size and baseline hemoglobin concentration). There was a gene dose effect according to the number of minor alleles in the genotype; carriers of the minor allele bled 17% (GT) and 54% (TT) more than wild type (GG) genotypes, respectively (p = 0.01). Carriers of the minor allele also had longer activated partial thromboplastin times (p = 0.0023) and increased fresh frozen plasma transfusion (p = 0.03) compared with wild type.
  
  
  CONCLUSIONS
  The authors found a dose-related association between the 98T E-selectin polymorphism and bleeding after cardiac surgery, independent of and additive to standard clinical risk factors.
authors.affiliation: Department of Anesthesiology, Duke University Medical Center, Durham, NC 27710, USA. welsb001@mc.duke.edu
authors.forename: Ian J
authors.initials: IJ
authors.lastname: Welsby
authors.forename: Mihai V
authors.initials: MV
authors.lastname: Podgoreanu
authors.forename: Barbara
authors.initials: B
authors.lastname: Phillips-Bute
authors.forename: Richard
authors.initials: R
authors.lastname: Morris
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Mathew
authors.forename: Peter K
authors.initials: PK
authors.lastname: Smith
authors.forename: Mark F
authors.initials: MF
authors.lastname: Newman
authors.forename: Debra A
authors.initials: DA
authors.lastname: Schwinn
authors.forename: Mark
authors.initials: M
authors.lastname: Stafford-Smith
mesh_terms: D000368:Aged; D000483:Alleles; D001772:Blood Cell Count; D001778:Blood Coagulation Disorders / Q000097:blood; D001780:Blood Coagulation Tests; D001803:Blood Transfusion; D006348:Cardiac Surgical Procedures; D002315:Cardiopulmonary Bypass; D015815:Cell Adhesion Molecules / Q000235:genetics; D016207:Cytokines / Q000235:genetics; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D004305:Dose-Response Relationship, Drug; D019040:E-Selectin / Q000235:genetics*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010314:Partial Thromboplastin Time; D011110:Polymorphism, Genetic; D019106:Postoperative Hemorrhage / Q000453:epidemiology* / Q000235:genetics*; D012044:Regression Analysis; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D015815:Cell Adhesion Molecules; D016207:Cytokines; D019040:E-Selectin; D004247:DNA