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Genetic variants in P-selection and C-reactive protein influence susceptibility to cognitive decline after cardiac surgery

Domenii publicaţii > Ştiinţe medicale + Tipuri publicaţii > Articol în revistã ştiinţificã

Autori: Mathew JP, Podgoreanu MV (co-first author), Grocott HP, White WD, Morris RW, Stafford- Smith M, Mackensen GB, Rinder CS, Blumenthal JA, Schwinn DA, Newman MF

Editorial: Journal of the American College of Cardiology, 49(19), p.1934-42, 2007.

Rezumat:

BJECTIVES: 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.

Cuvinte cheie: cognitive decline, single nucleotide polymorphisms, genetic association, inflammation

URL: http://www.ncbi.nlm.nih.gov/pubmed/17498578?ordinalpos=11&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum