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Published on: September 11, 2017
Posttraumatic Brain Injury Cognitive Performance Is Moderated by Variation Within ANKK1 and DRD2 Genes
Michelle D Failla1, John M Myrga, Joseph H Ricker
1Center for Neuroscience (Drs Failla, Dixon, and Wagner), Department of Physical Medicine and Rehabilitation, School of Medicine (Drs Failla, Dixon, and Wagner and Mr Myrga), and Department of Neurological Surgery, School of Medicine (Dr Dixon), Department of Human Genetics, School of Public Health (Dr Conley), Department of Health Promotion & Development, School of Nursing (Dr Conley), and Safar Center for Resuscitation Research (Drs Wagner and Dixon), University of Pittsburgh, Pittsburgh, Pennsylvania; Department of Rehabilitation Medicine, New York University, School of Medicine, New York (Dr Ricker); and Pittsburgh VA Healthcare System, Pittsburgh, Pennsylvania (Dr Dixon).
Objective:
As dopamine neurotransmission impacts cognition, we hypothesized that variants in the linked dopamine D2 receptor (DRD2) and ankyrin repeat and kinase domain (ANKK1) genes might account for some individual variability in cognitive recovery following traumatic brain injury (TBI).
Participants:
Prospective cohort of 108 survivors of severe TBI, recruited consecutively from a level 1 trauma center.
Design:
We examined relationships between DRD2 genetic variation and functional recovery at 6 and 12 months post-TBI.
Main Measures:
Cognitive performance was evaluated using 8 neuropsychological tests targeting different cognitive domains. An overall cognitive composite was developed using normative data. We also assessed functional cognition, depression status, and global outcome. Subjects were genotyped for 6 DRD2 tagging single-nucleotide polymorphisms and Taq1A within ANKK1.
Results:
ANKK1 Taq1A heterozygotes performed better than homozygotes across several cognitive domains at both time points postinjury. When adjusting for age, Glasgow Coma Scale score, and education, the Taq1A (ANKK1) and rs6279 (DRD2) variants were associated with overall composite scores at 6 months post-TBI (P = .0453 and P = .0452, respectively). At 12 months, only Taq1A remained a significant genetic predictor of cognition (P = .0128). Following multiple-comparisons correction, there were no significant associations between examined genetic variants and functional cognition, depression status, and global outcome.
Conclusion:
These data suggest that genetic variation within DRD2 influences cognitive recovery post-TBI. Understanding genetic influences on dopaminergic systems post-TBI may impact current treatment paradigms.
