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Research Paper|Volume 9, Issue 4|pp 1293—1306

Functional human GRIN2B promoter polymorphism and variation of mental processing speed in older adults

Yang Jiang1,3, Ming Kuan Lin2, Gregory A. Jicha3,4, Xiuhua Ding3,5, Sabrina L. McIlwrath1, David W. Fardo3,5, Lucas S. Broster1, Frederick A. Schmitt3,4, Richard Kryscio3,5, Robert H. Lipsky2,6
  • 1Department of Behavioral Science, University of Kentucky, Lexington, KY 40536, USA
  • 2Department of Molecular Neuroscience, the Krasnow Institute for Advanced Study, George Mason University, Fairfax, VA 22030, USA
  • 3Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY 40536, USA
  • 4Department of Neurology, University of Kentucky, Lexington, KY 40536, USA
  • 5Departments of Statistics and Biostatistics, University of Kentucky, Lexington, KY 40536, USA
  • 6Department of Neurosciences, Inova Neuroscience Institute, Inova Health System, Falls Church, VA 22042, USA

* * Equal contribution

Received: March 10, 2017Accepted: April 17, 2017Published: April 24, 2017
https://doi.org/10.18632/aging.101228

Copyright: © 2017 Jiang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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.