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Functional (GT)n polymorphisms in promoter region of N-methyl-d-aspartate receptor 2A subunit (GRIN2A) gene affect hippocampal and amygdala volumes

journal contribution
posted on 01.04.2010, 00:00 authored by H Inoue, H Yamasue, M Tochigi, M Suga, Y Iwayama, O Abe, H Yamada, Mark RogersMark Rogers, S Aoki, T Kato, T Sasaki, T Yoshikawa, K Kasai
The glutamate system including N-methyl-d-aspartate (NMDA) affects synaptic formation, plasticity and maintenance. Recent studies have shown a variable (GT)n polymorphism in the promoter region of the NMDA subunit gene (GRIN2A) and a length-dependent inhibition of transcriptional activity by the (GT)n repeat. In the present study, we examined whether the GRIN2A polymorphism is associated with regional brain volume especially in medial temporal lobe structures, in which the NMDA-dependent synaptic processes have been most extensively studied. Gray matter regions of interest (ROIs) for the bilateral amygdala and hippocampus were outlined manually on the magnetic resonance images of 144 healthy individuals. In addition, voxel-based morphometry (VBM) was conducted to explore the association of genotype with regional gray matter volume from everywhere in the brain in the same sample. The manually measured hippocampal and amygdala volumes were significantly larger in subjects with short allele carriers (n = 89) than in those with homozygous long alleles (n = 55) when individual differences in intracranial volume were accounted for. The VBM showed no significant association between the genotype and regional gray matter volume in any brain region. These findings suggest that the functional GRIN2A (GT)n polymorphism could weakly but significantly impact on human medial temporal lobe volume in a length-dependent manner, providing in vivo evidence of the role of the NMDA receptor in human brain development.

History

Journal

Genes, brain and behavior

Volume

9

Issue

3

Pagination

269 - 275

Publisher

Wiley - Blackwell Publishing

Location

Malden, Mass.

ISSN

1601-1848

eISSN

1601-183X

Language

eng

Publication classification

C1.1 Refereed article in a scholarly journal

Copyright notice

2010, The Authors