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  • Title: Genetic variants in P-selectin and C-reactive protein influence susceptibility to cognitive decline after cardiac surgery.
    Author: Mathew JP, Podgoreanu MV, Grocott HP, White WD, Morris RW, Stafford-Smith M, Mackensen GB, Rinder CS, Blumenthal JA, Schwinn DA, Newman MF, PEGASUS Investigative Team.
    Journal: J Am Coll Cardiol; 2007 May 15; 49(19):1934-42. PubMed ID: 17498578.
    Abstract:
    OBJECTIVES: 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.
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