Inducible nitric oxide synthase promoter polymorphism affords protection against cognitive dysfunction after carotid endarterectomy

Gene T. Yocum, John G. Gaudet, Susie So-Hyun Lee, Yaakov Stern, Lauren A. Teverbaugh, Robert R. Sciacca, Charles W. Emala, Donald O. Quest, Paul C. Mccormick, James F. Mckinsey, Nicholas J. Morrissey, Robert A. Solomon, E. Sander Connolly, Eric J. Heyer

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Background and Purpose-: 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. Conclusion-: 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.

Original languageEnglish (US)
Pages (from-to)1597-1603
Number of pages7
JournalStroke
Volume40
Issue number5
DOIs
StatePublished - May 1 2009
Externally publishedYes

Fingerprint

Carotid Endarterectomy
Nitric Oxide Synthase Type II
Tandem Repeat Sequences
Cognitive Dysfunction
Hand
Verbal Learning
Ischemic Preconditioning
Incidence
Wounds and Injuries
Carotid Arteries
Genetic Promoter Regions
Spine
Cohort Studies
Logistic Models
Alleles
Regression Analysis

Keywords

  • Carotid endarterectomy
  • Carotid stenosis
  • Cognitive impairment
  • Nitric oxide

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Clinical Neurology
  • Advanced and Specialized Nursing
  • Medicine(all)

Cite this

Inducible nitric oxide synthase promoter polymorphism affords protection against cognitive dysfunction after carotid endarterectomy. / Yocum, Gene T.; Gaudet, John G.; Lee, Susie So-Hyun; Stern, Yaakov; Teverbaugh, Lauren A.; Sciacca, Robert R.; Emala, Charles W.; Quest, Donald O.; Mccormick, Paul C.; Mckinsey, James F.; Morrissey, Nicholas J.; Solomon, Robert A.; Connolly, E. Sander; Heyer, Eric J.

In: Stroke, Vol. 40, No. 5, 01.05.2009, p. 1597-1603.

Research output: Contribution to journalArticle

Yocum, GT, Gaudet, JG, Lee, SS-H, Stern, Y, Teverbaugh, LA, Sciacca, RR, Emala, CW, Quest, DO, Mccormick, PC, Mckinsey, JF, Morrissey, NJ, Solomon, RA, Connolly, ES & Heyer, EJ 2009, 'Inducible nitric oxide synthase promoter polymorphism affords protection against cognitive dysfunction after carotid endarterectomy', Stroke, vol. 40, no. 5, pp. 1597-1603. https://doi.org/10.1161/STROKEAHA.108.541177
Yocum, Gene T. ; Gaudet, John G. ; Lee, Susie So-Hyun ; Stern, Yaakov ; Teverbaugh, Lauren A. ; Sciacca, Robert R. ; Emala, Charles W. ; Quest, Donald O. ; Mccormick, Paul C. ; Mckinsey, James F. ; Morrissey, Nicholas J. ; Solomon, Robert A. ; Connolly, E. Sander ; Heyer, Eric J. / Inducible nitric oxide synthase promoter polymorphism affords protection against cognitive dysfunction after carotid endarterectomy. In: Stroke. 2009 ; Vol. 40, No. 5. pp. 1597-1603.
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abstract = "Background and Purpose-: 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. Conclusion-: 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.",
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AU - Yocum, Gene T.

AU - Gaudet, John G.

AU - Lee, Susie So-Hyun

AU - Stern, Yaakov

AU - Teverbaugh, Lauren A.

AU - Sciacca, Robert R.

AU - Emala, Charles W.

AU - Quest, Donald O.

AU - Mccormick, Paul C.

AU - Mckinsey, James F.

AU - Morrissey, Nicholas J.

AU - Solomon, Robert A.

AU - Connolly, E. Sander

AU - Heyer, Eric J.

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N2 - Background and Purpose-: 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. Conclusion-: 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.

AB - Background and Purpose-: 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. Conclusion-: 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.

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KW - Carotid stenosis

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