title: Inducible nitric oxide synthase promoter polymorphism affords protection against cognitive dysfunction after carotid endarterectomy.
abstract: OBJECTIVE
  Cognitive dysfunction occurs in 9% to 23% of patients during the first month after carotid endarterectomy (CEA). A 4-basepair (AAAT) tandem repeat polymorphism (either 3 or 4 repeats) has been described in the promoter region of inducible nitric oxide synthase (iNOS), a gene with complex roles in ischemic injury and preconditioning against ischemic injury. We investigated whether the 4-repeat variant (iNOS(+)) affects the incidence of cognitive dysfunction after CEA.
  
  
  METHODS
  One-hundred eighty-five CEA and 60 spine surgery (control) subjects were included in this nested cohort analysis. Subjects underwent a battery of 7 neuropsychometric tests before and 1 day and 1 month after surgery. Multivariate logistic regression analyses were performed to determine if the iNOS promoter variant was independently associated with the incidence of cognitive dysfunction at 1 day and 1 month. Further, all right-hand-dominant CEA subjects were grouped by operative side and performance on each test was compared between iNOS(+) and iNOS(-) groups.
  
  
  RESULTS
  Forty-four of 185 CEA subjects had at least 1 iNOS promoter allele containing 4 copies of the tandem repeat (iNOS(+)). iNOS(+) status was significantly protective against moderate/severe cognitive dysfunction 1 month after CEA. Right-hand-dominant iNOS(+) CEA subjects undergoing left-side CEA performed significantly better than iNOS(-) subjects on a verbal learning test and those undergoing right-side CEA performed significantly better on a test of visuospatial function.
  
  
  CONCLUSIONS
  We demonstrate an iNOS promoter polymorphism variant provides protection against moderate/severe cognitive dysfunction 1 month after CEA. Further, this protection appears to involve cognitive domains localized ipsilateral to the operative carotid artery.
authors.affiliation: Department of Anesthesiology, Columbia University, New York, NY 10032, USA.
authors.forename: Gene T
authors.initials: GT
authors.lastname: Yocum
authors.forename: John G
authors.initials: JG
authors.lastname: Gaudet
authors.forename: Susie S
authors.initials: SS
authors.lastname: Lee
authors.forename: Yaakov
authors.initials: Y
authors.lastname: Stern
authors.forename: Lauren A
authors.initials: LA
authors.lastname: Teverbaugh
authors.forename: Robert R
authors.initials: RR
authors.lastname: Sciacca
authors.forename: Charles W
authors.initials: CW
authors.lastname: Emala
authors.forename: Donald O
authors.initials: DO
authors.lastname: Quest
authors.forename: Paul C
authors.initials: PC
authors.lastname: McCormick
authors.forename: James F
authors.initials: JF
authors.lastname: McKinsey
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Morrissey
authors.forename: Robert A
authors.initials: RA
authors.lastname: Solomon
authors.forename: E Sander
authors.initials: ES
authors.lastname: Connolly
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Heyer
mesh_terms: D000368:Aged; D000483:Alleles; D001057:Apolipoproteins E / Q000235:genetics; D003072:Cognition Disorders / Q000209:etiology* / Q000235:genetics* / Q000523:psychology; D016894:Endarterectomy, Carotid / Q000009:adverse effects*; D005260:Female; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D008297:Male; D009483:Neuropsychological Tests; D009569:Nitric Oxide / Q000096:biosynthesis / Q000502:physiology; D052247:Nitric Oxide Synthase Type II / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics; D011183:Postoperative Complications / Q000523:psychology*; D011401:Promoter Regions, Genetic / Q000235:genetics*
chemical_list: D001057:Apolipoproteins E; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II