Posttraumatic Brain Injury Cognitive Performance Is Moderated by Variation Within ANKK1 and DRD2 Genes. Issue 6 (November 2015)

• Record Type: Journal Article
• Authors: Failla, Michelle D.; Myrga, John M.; Ricker, Joseph H.; Dixon, C. Edward; Conley, Yvette P.; Wagner, Amy K.
• Is Part Of: Journal of head trauma rehabilitation. Volume 30:Issue 6(2015:Nov./Dec.)
• Publication Date: 2015-11
• Subjects: ANKK1 -- cognitive deficits -- DRD2 -- dopamine -- genetic variation -- Rehabilomics -- traumatic brain injury; Brain damage -- Patients -- Rehabilitation -- Periodicals; Brain damage -- Periodicals; 617.4810443
• DOI: 10.1097/HTR.0000000000000118
• Languages: English
• ISSNs: 0885-9701

Abstract

Abstract : 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.