DRD2 C957T polymorphism is associated with improved 6-month verbal learning following traumatic brain injury
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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.
KeywordsTraumatic brain injury Genetic factors Cognition Outcome measures Human studies
The authors would like to thank the following contributors to the development of the TRACK-TBI database and repositories by organization and alphabetical order by last name—One Mind for Research: General Peter Chiarelli, US Army (Ret.), and Garen Staglin, MBA; QuesGen Systems, Inc.: Vibeke Brinck, MS, and Michael Jarrett, MBA; and Thomson Reuters: Sirimon O’Charoen, PhD.
Compliance with ethical standards
This work was supported by the following grants: NIH RC2 NS069409, NIH RC2 NS069409-02S1, NIH U01 NS086090-01, DOD W81XWH-13-1-0441, and DOD W81XWH-14-2-0176 (to G.T.M.)
Conflict of interest
The authors declare that they have no conflicts of interest.
Informed consent was obtained from all individual participants included in the study.
Research involving human participants
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.
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