Article

Genetic Variants in P-Selectin and C-Reactive Protein Influence Susceptibility to Cognitive Decline After Cardiac Surgery

Department of Anesthesiology, Duke University, Durham, North Carolina, United States
Journal of the American College of Cardiology (Impact Factor: 16.5). 06/2007; 49(19):1934-42. DOI: 10.1016/j.jacc.2007.01.080
Source: PubMed

ABSTRACT

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).
Cognitive decline is a common complication of coronary artery bypass graft (CABG) surgery and is associated with a reduced quality of life.
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.
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.
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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    • "However, it is similar to the prospective predictive power (∼5%) of the serum P-selectin levels on the intersubject variability in the carotid intima–media thickness measured 5 years later. Our findings also support the hypothesis of a direct genetic relationship between P-selectin expression and cerebral atrophy as proposed by two studies that demonstrated neurocognitive differences in the elderly carriers of 1087 allele of this gene (Mathew et al., 2007; Gunstad et al., 2009). However, allele-specific PCR validation will be necessary to name the specific genetic variants that are responsible for this association. "
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