Genetic variants in P-selectin and C-reactive protein influence susceptibility to cognitive decline after cardiac surgery.
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.
Mathew
Joseph P
JP
Department of Anesthesiology, Duke University Medical Center, Durham, North Carolina.
Podgoreanu
Mihai V
MV
Grocott
Hilary P
HP
White
William D
WD
Morris
Richard W
RW
Stafford-Smith
Mark
M
Mackensen
G Burkhard
GB
Rinder
Christine S
CS
Blumenthal
James A
JA
Schwinn
Debra A
DA
Newman
Mark F
MF
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
D019007:P-Selectin; D002097:C-Reactive Protein