Research Paper Volume 9, Issue 4 pp 1293—1306
Functional human GRIN2B promoter polymorphism and variation of mental processing speed in older adults
- 1 Department of Behavioral Science, University of Kentucky, Lexington, KY 40536, USA
- 2 Department of Molecular Neuroscience, the Krasnow Institute for Advanced Study, George Mason University, Fairfax, VA 22030, USA
- 3 Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY 40536, USA
- 4 Department of Neurology, University of Kentucky, Lexington, KY 40536, USA
- 5 Departments of Statistics and Biostatistics, University of Kentucky, Lexington, KY 40536, USA
- 6 Department of Neurosciences, Inova Neuroscience Institute, Inova Health System, Falls Church, VA 22042, USA
Received: March 10, 2017 Accepted: April 17, 2017 Published: April 24, 2017
https://doi.org/10.18632/aging.101228How to Cite
Abstract
We investigated the role of a single nucleotide polymorphism rs3764030 (G>A) within the human GRIN2B promoter in mental processing speed in healthy, cognitively intact, older adults. In vitro DNA-binding and reporter gene assays of different allele combinations in transfected cells showed that the A allele was a gain-of-function variant associated with increasing GRIN2B mRNA levels. We tested the hypothesis that individuals with A allele will have better memory performance (i.e. faster reaction times) in older age. Twenty-eight older adults (ages 65-86) from a well-characterized longitudinal cohort were recruited and performed a modified delayed match-to-sample task. The rs3764030 polymorphism was genotyped and participants were grouped based on the presence of the A allele into GG and AA/AG. Carriers of the A allele maintained their speed of memory retrieval over age compared to GG carriers (p = 0.026 slope of the regression line between AA and AG versus GG groups). To validate the results, 12 older adults from the same cohort participated in a different version of the short-term memory task. Reaction times were significantly slower with age in older adults with G allele (p < 0.001). These findings support a role for rs3764030 in maintaining faster mental processing speed over aging.