title: Genetic variants in P-selectin and C-reactive protein influence susceptibility to cognitive decline after cardiac surgery.
abstract: OBJECTIVE
  We hypothesized that candidate gene polymorphisms in biologic pathways regulating inflammation, cell matrix adhesion/interaction, coagulation-thrombosis, lipid metabolism, and vascular reactivity are associated with postoperative cognitive deficit (POCD).
  
  
  BACKGROUND
  Cognitive decline is a common complication of coronary artery bypass graft (CABG) surgery and is associated with a reduced quality of life.
  
  
  METHODS
  In a prospective cohort study of 513 patients (86% European American) undergoing CABG surgery with cardiopulmonary bypass, a panel of 37 single-nucleotide polymorphisms (SNPs) was genotyped by mass spectrometry. Association between these SNPs and cognitive deficit at 6 weeks after surgery was tested using multiple logistic regression accounting for age, level of education, baseline cognition, and population structure. Permutation analysis was used to account for multiple testing.
  
  
  RESULTS
  We found that minor alleles of the CRP 1059G/C SNP (odds ratio [OR] 0.37, 95% confidence interval [CI] 0.16 to 0.78; p = 0.013) and the SELP 1087G/A SNP (OR 0.51, 95% CI 0.30 to 0.85; p = 0.011) were associated with a reduction in cognitive deficit in European Americans (n = 443). The absolute risk reduction in the observed incidence of POCD was 20.6% for carriers of the CRP 1059C allele and 15.2% for carriers of the SELP 1087A allele. Perioperative serum C-reactive protein (CRP) and degree of platelet activation were also significantly lower in patients with a copy of the minor alleles, providing biologic support for the observed allelic association.
  
  
  CONCLUSIONS
  The results suggest a contribution of P-selectin and CRP genes in modulating susceptibility to cognitive decline after cardiac surgery, with potential implications for identifying populations at risk who might benefit from targeted perioperative antiinflammatory strategies.
authors.affiliation: Department of Anesthesiology, Duke University Medical Center, Durham, North Carolina.
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Mathew
authors.forename: Mihai V
authors.initials: MV
authors.lastname: Podgoreanu
authors.forename: Hilary P
authors.initials: HP
authors.lastname: Grocott
authors.forename: William D
authors.initials: WD
authors.lastname: White
authors.forename: Richard W
authors.initials: RW
authors.lastname: Morris
authors.forename: Mark
authors.initials: M
authors.lastname: Stafford-Smith
authors.forename: G Burkhard
authors.initials: GB
authors.lastname: Mackensen
authors.forename: Christine S
authors.initials: CS
authors.lastname: Rinder
authors.forename: James A
authors.initials: JA
authors.lastname: Blumenthal
authors.forename: Debra A
authors.initials: DA
authors.lastname: Schwinn
authors.forename: Mark F
authors.initials: MF
authors.lastname: Newman
mesh_terms: D000368:Aged; D002097:C-Reactive Protein / Q000235:genetics*; D003072:Cognition Disorders / Q000453:epidemiology / Q000235:genetics*; D015331:Cohort Studies; D001026:Coronary Artery Bypass / Q000009:adverse effects*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D019007:P-Selectin / Q000235:genetics*; D011110:Polymorphism, Genetic
chemical_list: D019007:P-Selectin; D002097:C-Reactive Protein