neurogenetics

, Volume 17, Issue 1, pp 31–41 | Cite as

COMT Val158Met polymorphism is associated with nonverbal cognition following mild traumatic brain injury

  • Ethan A. Winkler
  • John K. Yue
  • Thomas W. McAllister
  • Nancy R. Temkin
  • Sam S. Oh
  • Esteban G. Burchard
  • Donglei Hu
  • Adam R. Ferguson
  • Hester F. Lingsma
  • John F. Burke
  • Marco D. Sorani
  • Jonathan Rosand
  • Esther L. Yuh
  • Jason Barber
  • Phiroz E. Tarapore
  • Raquel C. Gardner
  • Sourabh Sharma
  • Gabriela G. Satris
  • Celeste Eng
  • Ava M. Puccio
  • Kevin K. W. Wang
  • Pratik Mukherjee
  • Alex B. Valadka
  • David O. Okonkwo
  • Ramon Diaz-Arrastia
  • Geoffrey T. Manley
  • the TRACK-TBI Investigators
Original Article

Abstract

Mild traumatic brain injury (mTBI) results in variable clinical outcomes, which may be influenced by genetic variation. A single-nucleotide polymorphism in catechol-o-methyltransferase (COMT), an enzyme which degrades catecholamine neurotransmitters, may influence cognitive deficits following moderate and/or severe head trauma. However, this has been disputed, and its role in mTBI has not been studied. Here, we utilize the Transforming Research and Clinical Knowledge in Traumatic Brain Injury Pilot (TRACK-TBI Pilot) study to investigate whether the COMT Val158Met polymorphism influences outcome on a cognitive battery 6 months following mTBI—Wechsler Adult Intelligence Test Processing Speed Index Composite Score (WAIS-PSI), Trail Making Test (TMT) Trail B minus Trail A time, and California Verbal Learning Test, Second Edition Trial 1–5 Standard Score (CVLT-II). All patients had an emergency department Glasgow Coma Scale (GCS) of 13–15, no acute intracranial pathology on head CT, and no polytrauma as defined by an Abbreviated Injury Scale (AIS) score of ≥3 in any extracranial region. Results in 100 subjects aged 40.9 (SD 15.2) years (COMT Met158/Met158 29 %, Met158/Val158 47 %, Val158/Val158 24 %) show that the COMT Met158 allele (mean 101.6 ± SE 2.1) associates with higher nonverbal processing speed on the WAIS-PSI when compared to Val158/Val158 homozygotes (93.8 ± SE 3.0) after controlling for demographics and injury severity (mean increase 7.9 points, 95 % CI [1.4 to 14.3], p = 0.017). The COMT Val158Met polymorphism did not associate with mental flexibility on the TMT or with verbal learning on the CVLT-II. Hence, COMT Val158Met may preferentially modulate nonverbal cognition following uncomplicated mTBI.

Registry: ClinicalTrials.gov Identifier NCT01565551

Keywords

Traumatic brain injury Genetic factors Cognitive function Outcome measures Human studies 

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Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Ethan A. Winkler
    • 1
    • 2
  • John K. Yue
    • 1
    • 2
  • Thomas W. McAllister
    • 3
  • Nancy R. Temkin
    • 4
  • Sam S. Oh
    • 5
  • Esteban G. Burchard
    • 5
  • Donglei Hu
    • 5
  • Adam R. Ferguson
    • 1
    • 2
  • Hester F. Lingsma
    • 6
  • John F. Burke
    • 1
    • 2
  • Marco D. Sorani
    • 1
    • 2
  • Jonathan Rosand
    • 7
    • 8
  • Esther L. Yuh
    • 2
    • 9
  • Jason Barber
    • 4
  • Phiroz E. Tarapore
    • 1
    • 2
  • Raquel C. Gardner
    • 7
    • 10
  • Sourabh Sharma
    • 1
    • 2
  • Gabriela G. Satris
    • 1
    • 2
  • Celeste Eng
    • 5
  • Ava M. Puccio
    • 11
  • Kevin K. W. Wang
    • 12
  • Pratik Mukherjee
    • 2
    • 9
  • Alex B. Valadka
    • 13
  • David O. Okonkwo
    • 11
  • Ramon Diaz-Arrastia
    • 14
    • 15
  • Geoffrey T. Manley
    • 1
    • 2
  • the TRACK-TBI Investigators
  1. 1.Department of Neurological SurgeryUniversity of California, San FranciscoSan FranciscoUSA
  2. 2.Brain and Spinal Injury CenterSan Francisco General HospitalSan FranciscoUSA
  3. 3.Department of PsychiatryIndiana University School of MedicineIndianapolisUSA
  4. 4.Departments of Neurological Surgery and BiostatisticsUniversity of WashingtonSeattleUSA
  5. 5.Department of Bioengineering and Therapeutic SciencesUniversity of California, San FranciscoSan FranciscoUSA
  6. 6.Department of Public HealthErasmus Medical CenterRotterdamThe Netherlands
  7. 7.Department of NeurologyHarvard Medical SchoolBostonUSA
  8. 8.Program in Medical and Population GeneticsThe Broad Institute of MIT and HarvardCambridgeUSA
  9. 9.Department of RadiologyUniversity of California, San FranciscoSan FranciscoUSA
  10. 10.Department of NeurologySan Francisco Veterans Administration Medical CenterSan FranciscoUSA
  11. 11.Department of Neurological SurgeryUniversity of Pittsburgh Medical CenterPittsburghUSA
  12. 12.Center for Neuroproteomics and Biomarkers Research, Departments of Psychiatry and NeuroscienceUniversity of FloridaGainesvilleUSA
  13. 13.Seton Brain and Spine InstituteAustinUSA
  14. 14.Department of NeurologyUniformed Services University of the Health SciencesBethesdaUSA
  15. 15.Center for Neuroscience and Regenerative MedicineBethesdaUSA

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