DRD2 C957T polymorphism is associated with improved 6-month verbal learning following traumatic brain injury.
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.
Department of Neurological Surgery, University of California, San Francisco, 1001 Potrero Avenue, Building 1, Room 101, San Francisco, CA, 94110, USA.|Brain and Spinal Injury Center, San Francisco General Hospital, San Francisco, CA, USA.
John K
JK
Yue
Department of Neurological Surgery, University of California, San Francisco, 1001 Potrero Avenue, Building 1, Room 101, San Francisco, CA, 94110, USA.|Brain and Spinal Injury Center, San Francisco General Hospital, San Francisco, CA, USA.
Ethan A
EA
Winkler
Department of Neurological Surgery, University of California, San Francisco, 1001 Potrero Avenue, Building 1, Room 101, San Francisco, CA, 94110, USA.|Brain and Spinal Injury Center, San Francisco General Hospital, San Francisco, CA, USA.
Jonathan W
JW
Rick
Department of Neurological Surgery, University of California, San Francisco, 1001 Potrero Avenue, Building 1, Room 101, San Francisco, CA, 94110, USA.|Brain and Spinal Injury Center, San Francisco General Hospital, San Francisco, CA, USA.
John F
JF
Burke
Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, USA.
Thomas W
TW
McAllister
Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA, USA.
Sam S
SS
Oh
Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA, USA.
Esteban G
EG
Burchard
Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA, USA.
Donglei
D
Hu
Department of Neurology, Harvard Medical School, Boston, MA, USA.|Program in Medical and Population Genetics, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Jonathan
J
Rosand
Department of Neurological Surgery and Biostatistics, University of Washington, Seattle, WA, USA.
Nancy R
NR
Temkin
Department of Emergency Medicine, Johns Hopkins University, Baltimore, MD, USA.
Frederick K
FK
Korley
Department of Neurological Surgery, University of California, San Francisco, 1001 Potrero Avenue, Building 1, Room 101, San Francisco, CA, 94110, USA.|Brain and Spinal Injury Center, San Francisco General Hospital, San Francisco, CA, USA.
Marco D
MD
Sorani
Department of Neurological Surgery, University of California, San Francisco, 1001 Potrero Avenue, Building 1, Room 101, San Francisco, CA, 94110, USA.|Brain and Spinal Injury Center, San Francisco General Hospital, San Francisco, CA, USA.
Adam R
AR
Ferguson
Department of Public Health, Erasmus Medical Center, Rotterdam, The Netherlands.
Hester F
HF
Lingsma
Department of Neurological Surgery, University of California, San Francisco, 1001 Potrero Avenue, Building 1, Room 101, San Francisco, CA, 94110, USA.|Brain and Spinal Injury Center, San Francisco General Hospital, San Francisco, CA, USA.
Sourabh
S
Sharma
Department of Neurological Surgery, University of California, San Francisco, 1001 Potrero Avenue, Building 1, Room 101, San Francisco, CA, 94110, USA.|Brain and Spinal Injury Center, San Francisco General Hospital, San Francisco, CA, USA.
Caitlin K
CK
Robinson
Department of Neurological Surgery, University of California, San Francisco, 1001 Potrero Avenue, Building 1, Room 101, San Francisco, CA, 94110, USA.|Department of Radiology, University of California, San Francisco, San Francisco, CA, USA.
Esther L
EL
Yuh
Department of Neurological Surgery, University of California, San Francisco, 1001 Potrero Avenue, Building 1, Room 101, San Francisco, CA, 94110, USA.|Brain and Spinal Injury Center, San Francisco General Hospital, San Francisco, CA, USA.
Phiroz E
PE
Tarapore
Center for Neuroproteomics and Biomarkers Research, Department of Psychiatry and Neuroscience, University of Florida, Gainesville, FL, USA.
Kevin K W
KK
Wang
Department of Neurological Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
Ava M
AM
Puccio
Department of Neurological Surgery, University of California, San Francisco, 1001 Potrero Avenue, Building 1, Room 101, San Francisco, CA, 94110, USA.|Department of Radiology, University of California, San Francisco, San Francisco, CA, USA.
Pratik
P
Mukherjee
Department of Neurology, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.|Center for Neuroscience and Regenerative Medicine, Bethesda, MD, USA.
Ramon
R
Diaz-Arrastia
Department of Rehabilitation Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Wayne A
WA
Gordon
Department of Neurological Surgery, Virginia Commonwealth University, Richmond, VA, USA.
Alex B
AB
Valadka
Department of Neurological Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
David O
DO
Okonkwo
Department of Neurological Surgery, University of California, San Francisco, 1001 Potrero Avenue, Building 1, Room 101, San Francisco, CA, 94110, USA. manleyg@neurosurg.ucsf.edu.|Brain and Spinal Injury Center, San Francisco General Hospital, San Francisco, CA, USA. manleyg@neurosurg.ucsf.edu.
Geoffrey T
GT
Manley
D000328:Adult; D000070642:Brain Injuries, Traumatic / Q000235:genetics / Q000523:psychology / Q000534:rehabilitation*; D016022:Case-Control Studies; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009473:Neuronal Plasticity / Q000235:genetics*; D010865:Pilot Projects; D020641:Polymorphism, Single Nucleotide; D017448:Receptors, Dopamine D2 / Q000235:genetics*; D014706:Verbal Learning / Q000502:physiology*
C581293:DRD2 protein, human; D017448:Receptors, Dopamine D2
Cognition; Genetic factors; Human studies; Outcome measures; Traumatic brain injury