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

Yang Jiang, Ming Kuan Lin, Gregory A. Jicha, Xiuhua Ding, Sabrina L. McIlwrath, David W. Fardo, Lucas S. Broster, Frederick A. Schmitt, Richard Kryscio, Robert H. Lipsky

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


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 gainof- 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.

Original languageEnglish
Pages (from-to)1293-1306
Number of pages14
Issue number4
StatePublished - 2017

Bibliographical note

Funding Information:
This work was founded by National Institute on Aging K01AG000986; P30AG028383; Virginia Center on Aging (RHL), Inova Research Foundation, George Mason Research Foundation, (RHL, ML)


  • Cognitive aging
  • Functional polymorphism
  • GRIN2B gene
  • NMDA receptor
  • Short-term memory
  • Working memory retrieval

ASJC Scopus subject areas

  • Aging
  • Cell Biology


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