title: Phosphodiesterase 4D single-nucleotide polymorphism 83 and cognitive dysfunction in carotid endarterectomy patients.
abstract: Phosphodiesterase 4D (PDE4D), through the regulation of cyclic AMP, modulates inflammation and other processes that affect atherosclerosis and stroke. A PDE4D polymorphism, single-nucleotide polymorphism (SNP) 83 (rs966221), is associated with ischemic stroke. The association of SNP 83 with postoperative cognitive dysfunction has never been investigated.
  
  
  
  To determine whether SNP 83 is associated with cognitive dysfunction 1 day and 1 month following carotid endarterectomy (CEA).
  
  
  
  Three hundred fourteen patients with high-grade carotid stenosis scheduled for CEA consented to participate in this single-center cohort study of cognitive dysfunction.
  
  
  
  Patients with the C/C genotype of SNP 83 exhibited significantly more cognitive dysfunction at 1 day (29.7%) than the C/T (15.8%, P = .008) and T/T (12.7%, P = .01) genotypes. In a multivariate logistic regression model, C/T and T/T genotypes were both associated with significantly decreased odds of cognitive dysfunction compared with the C/C genotype (odds ratio, 0.45 [0.24-0.83], P = .01 and odds ratio, 0.33 [0.12-0.77], P = .02). There were no significant associations at 1 month.
  
  
  
  The C/C genotype of SNP 83 is significantly associated with the highest incidence of cognitive dysfunction 1 day following CEA in comparison with the C/T and T/T genotypes. This PDE4D genotype may lead to accelerated cyclic AMP degradation and subsequently elevated inflammation 1 day after CEA. These observations, in conjunction with previous studies, suggest that elevated inflammatory states may be partially responsible for the development of cognitive dysfunction after CEA, but more investigation is required.
authors.affiliation: *Department of Anesthesiology, Columbia University, New York, New York; ‡Department of Neurology, Columbia University, New York, New York; §Department of Neurological Surgery, Columbia University, New York, New York.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Heyer
authors.forename: Joanna L
authors.initials: JL
authors.lastname: Mergeche
authors.forename: Justin T
authors.initials: JT
authors.lastname: Ward
authors.forename: Hani R
authors.initials: HR
authors.lastname: Malone
authors.forename: Christopher
authors.initials: C
authors.lastname: Kellner
authors.forename: Samuel S
authors.initials: SS
authors.lastname: Bruce
authors.forename: E Sander
authors.initials: ES
authors.lastname: Connolly
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016893:Carotid Stenosis / Q000235:genetics / Q000601:surgery; D003072:Cognition Disorders / Q000209:etiology* / Q000235:genetics*; D015331:Cohort Studies; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4 / Q000235:genetics*; D016894:Endarterectomy, Carotid; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D009483:Neuropsychological Tests; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011183:Postoperative Complications / Q000235:genetics*; D012044:Regression Analysis; D018709:Statistics, Nonparametric
chemical_list: D054703:Cyclic Nucleotide Phosphodiesterases, Type 4