Influence of PARP-1 polymorphisms in patients after traumatic brain injury

Ajit A. Sarnaik, Yvette P. Conley, David O. Okonkwo, Taura L. Barr, Ericka L. Fink, Csaba Szabo, Patrick M. Kochanek, Robert S B Clark

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Poly(ADP-ribose) polymerase-1 (PARP-1) plays an important role in the cellular response to stress and DNA damage. However, excessive activity of PARP-1 exacerbates brain injury via NAD+ depletion and energy failure. The purpose of this study was to determine if tagging single nucleotide polymorphisms (tSNPs) covering multiple regions of the PARP-1 gene are related to outcome after traumatic brain injury (TBI) in humans. DNA from 191 adult patients with severe TBI was assayed for four tSNPs corresponding to haplotype blocks spanning the PARP-1 gene. Categorization as favorable or poor outcome was based on Glasgow Outcome Scale (GOS) score assigned at 6 months. PARP-1 enzyme activity was indirectly evaluated by quantifying poly-ADP-ribose (PAR)-modified proteins in cerebrospinal fluid (CSF) using an enzyme-linked immunosorbent assay. In multiple logistic regression analysis controlling for age, initial Glasgow Coma Scale score, and gender, the AA genotype of SNP rs3219119 was an independent predictor of favorable neurologic outcome. This SNP tags a haplotype block spanning the automodification and catalytic domains of the PARP-1 gene. SNP rs2271347 correlated with CSF PAR-modified protein level. This SNP, which did not correlate with outcome, tags a haplotype block spanning the promoter region of the PARP-1 gene. We conclude that after severe TBI in humans, a PARP-1 polymorphism within the automodification-catalytic domain is associated with neurological outcome, while a polymorphism within the promoter region was associated with CSF PAR-modified protein level. These findings must be replicated in a prospective study before the relevance of PARP-1 polymorphisms after TBI can be established.

Original languageEnglish (US)
Pages (from-to)465-471
Number of pages7
JournalJournal of Neurotrauma
Volume27
Issue number3
DOIs
StatePublished - Mar 1 2010

Fingerprint

Single Nucleotide Polymorphism
Poly Adenosine Diphosphate Ribose
Haplotypes
Genetic Promoter Regions
Genes
Cerebrospinal Fluid
Catalytic Domain
Glasgow Outcome Scale
Cerebrospinal Fluid Proteins
Glasgow Coma Scale
Poly (ADP-Ribose) Polymerase-1
Traumatic Brain Injury
NAD
Brain Injuries
Nervous System
DNA Damage
Proteins
Logistic Models
Enzyme-Linked Immunosorbent Assay
Genotype

Keywords

  • ADP-ribosyltransferase
  • Poly(ADP-ribose) polymerase
  • Poly-ADP-ribosylation
  • Traumatic brain injury

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Sarnaik, A. A., Conley, Y. P., Okonkwo, D. O., Barr, T. L., Fink, E. L., Szabo, C., ... Clark, R. S. B. (2010). Influence of PARP-1 polymorphisms in patients after traumatic brain injury. Journal of Neurotrauma, 27(3), 465-471. https://doi.org/10.1089/neu.2009.1171

Influence of PARP-1 polymorphisms in patients after traumatic brain injury. / Sarnaik, Ajit A.; Conley, Yvette P.; Okonkwo, David O.; Barr, Taura L.; Fink, Ericka L.; Szabo, Csaba; Kochanek, Patrick M.; Clark, Robert S B.

In: Journal of Neurotrauma, Vol. 27, No. 3, 01.03.2010, p. 465-471.

Research output: Contribution to journalArticle

Sarnaik, AA, Conley, YP, Okonkwo, DO, Barr, TL, Fink, EL, Szabo, C, Kochanek, PM & Clark, RSB 2010, 'Influence of PARP-1 polymorphisms in patients after traumatic brain injury', Journal of Neurotrauma, vol. 27, no. 3, pp. 465-471. https://doi.org/10.1089/neu.2009.1171
Sarnaik, Ajit A. ; Conley, Yvette P. ; Okonkwo, David O. ; Barr, Taura L. ; Fink, Ericka L. ; Szabo, Csaba ; Kochanek, Patrick M. ; Clark, Robert S B. / Influence of PARP-1 polymorphisms in patients after traumatic brain injury. In: Journal of Neurotrauma. 2010 ; Vol. 27, No. 3. pp. 465-471.
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