neurogenetics

, Volume 18, Issue 1, pp 29–38

DRD2 C957T polymorphism is associated with improved 6-month verbal learning following traumatic brain injury

  • John K. Yue
  • Ethan A. Winkler
  • Jonathan W. Rick
  • John F. Burke
  • Thomas W. McAllister
  • Sam S. Oh
  • Esteban G. Burchard
  • Donglei Hu
  • Jonathan Rosand
  • Nancy R. Temkin
  • Frederick K. Korley
  • Marco D. Sorani
  • Adam R. Ferguson
  • Hester F. Lingsma
  • Sourabh Sharma
  • Caitlin K. Robinson
  • Esther L. Yuh
  • Phiroz E. Tarapore
  • Kevin K.W. Wang
  • Ava M. Puccio
  • Pratik Mukherjee
  • Ramon Diaz-Arrastia
  • Wayne A. Gordon
  • Alex B. Valadka
  • David O. Okonkwo
  • Geoffrey T. Manley
  • TRACK-TBI Investigators
Original Article

DOI: 10.1007/s10048-016-0500-6

Cite this article as:
Yue, J.K., Winkler, E.A., Rick, J.W. et al. Neurogenetics (2017) 18: 29. doi:10.1007/s10048-016-0500-6
  • 193 Downloads

Abstract

Traumatic brain injury (TBI) often leads to heterogeneous clinical outcomes, which may be influenced by genetic variation. A single-nucleotide polymorphism (SNP) in the dopamine D2 receptor (DRD2) may influence cognitive deficits following TBI. However, part of the association with DRD2 has been attributed to genetic variability within the adjacent ankyrin repeat and kinase domain containing 1 protein (ANKK1). Here, we utilize the Transforming Research and Clinical Knowledge in Traumatic Brain Injury Pilot (TRACK-TBI Pilot) study to investigate whether a novel DRD2 C957T polymorphism (rs6277) influences outcome on a cognitive battery at 6 months following TBI—California Verbal Learning Test (CVLT-II), Wechsler Adult Intelligence Test Processing Speed Index Composite Score (WAIS-PSI), and Trail Making Test (TMT). Results in 128 Caucasian subjects show that the rs6277 T-allele associates with better verbal learning and recall on CVLT-II Trials 1–5 (T-allele carrier 52.8 ± 1.3 points, C/C 47.9 ± 1.7 points; mean increase 4.9 points, 95% confidence interval [0.9 to 8.8]; p = 0.018), Short-Delay Free Recall (T-carrier 10.9 ± 0.4 points, C/C 9.7 ± 0.5 points; mean increase 1.2 points [0.1 to 2.5]; p = 0.046), and Long-Delay Free Recall (T-carrier 11.5 ± 0.4 points, C/C 10.2 ± 0.5 points; mean increase 1.3 points [0.1 to 2.5]; p = 0.041) after adjusting for age, education years, Glasgow Coma Scale, presence of acute intracranial pathology on head computed tomography scan, and genotype of the ANKK1 SNP rs1800497 using multivariable regression. No association was found between DRD2 C947T and non-verbal processing speed (WAIS-PSI) or mental flexibility (TMT) at 6 months. Hence, DRD2 C947T (rs6277) may be associated with better performance on select cognitive domains independent of ANKK1 following TBI.

Keywords

Traumatic brain injury Genetic factors Cognition Outcome measures Human studies 

Funding information

Funder NameGrant NumberFunding Note
National Institute of Neurological Disorders and Stroke
  • RC2 NS069409
  • RC2 NS069409-02S1
  • U01 NS086090-01
U.S. Department of Defense
  • W81XWH-13-1-0441
  • W81XWH-14-2-0176

Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • John K. Yue
    • 1
    • 2
  • Ethan A. Winkler
    • 1
    • 2
  • Jonathan W. Rick
    • 1
    • 2
  • John F. Burke
    • 1
    • 2
  • Thomas W. McAllister
    • 3
  • Sam S. Oh
    • 4
  • Esteban G. Burchard
    • 4
  • Donglei Hu
    • 4
  • Jonathan Rosand
    • 5
    • 6
  • Nancy R. Temkin
    • 7
  • Frederick K. Korley
    • 8
  • Marco D. Sorani
    • 1
    • 2
  • Adam R. Ferguson
    • 1
    • 2
  • Hester F. Lingsma
    • 9
  • Sourabh Sharma
    • 1
    • 2
  • Caitlin K. Robinson
    • 1
    • 2
  • Esther L. Yuh
    • 1
    • 10
  • Phiroz E. Tarapore
    • 1
    • 2
  • Kevin K.W. Wang
    • 11
  • Ava M. Puccio
    • 12
  • Pratik Mukherjee
    • 1
    • 10
  • Ramon Diaz-Arrastia
    • 13
    • 14
  • Wayne A. Gordon
    • 15
  • Alex B. Valadka
    • 16
  • David O. Okonkwo
    • 12
  • Geoffrey T. Manley
    • 1
    • 2
  • 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.Department of Bioengineering and Therapeutic SciencesUniversity of California, San FranciscoSan FranciscoUSA
  5. 5.Department of NeurologyHarvard Medical SchoolBostonUSA
  6. 6.Program in Medical and Population GeneticsThe Broad Institute of MIT and HarvardCambridgeUSA
  7. 7.Department of Neurological Surgery and BiostatisticsUniversity of WashingtonSeattleUSA
  8. 8.Department of Emergency MedicineJohns Hopkins UniversityBaltimoreUSA
  9. 9.Department of Public HealthErasmus Medical CenterRotterdamThe Netherlands
  10. 10.Department of RadiologyUniversity of California, San FranciscoSan FranciscoUSA
  11. 11.Center for Neuroproteomics and Biomarkers Research, Department of Psychiatry and NeuroscienceUniversity of FloridaGainesvilleUSA
  12. 12.Department of Neurological SurgeryUniversity of Pittsburgh Medical CenterPittsburghUSA
  13. 13.Department of NeurologyUniformed Services University of the Health SciencesBethesdaUSA
  14. 14.Center for Neuroscience and Regenerative MedicineBethesdaUSA
  15. 15.Department of Rehabilitation MedicineIcahn School of Medicine at Mount SinaiNew YorkUSA
  16. 16.Department of Neurological SurgeryVirginia Commonwealth UniversityRichmondUSA

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