Genetic Variation in N-Methyl-D-Aspartate Receptor Subunit NR3A but Not NR3B Influences Susceptibility to Alzheimer’s Disease
Abstract
Background: The administration of memantine, an N-methyl-D-aspartate (NMDA) receptor antagonist, has clinically improved the cognitive function of patients with Alzheimer’s disease (AD), indicating that a disturbance in glutamatergic transmission might be involved in a predisposition to developing the disease. Aim: The potential association of polymorphisms in NMDA receptor subunits NR3A and NR3B, encoded by the GRIN3A and GRIN3B genes, with AD was investigated. Methods: We performed a case-control study. Two single nucleotide polymorphisms, 3104 G/A (rs10989563) and 3723 G/A (rs3739722), in the GRIN3A gene and 2 GRIN3B gene polymorphisms, 1210 C/T (rs4807399) and 1730 C/T (rs2240158), were studied. Results: Upon genotyping of the exonic polymorphism in the GRIN3A gene, the G allele was present at a higher rate than the A allele at position 3723 in AD patients compared with normal groups (p < 0.05). Three haplotypes (designated Ht1–3) were identified from these 2 polymorphisms (3104 G/A and 3723 G/A), and the distribution of Ht2 (AG) differed between AD patients and controls (p < 0.05). Additionally, from the 2 GRIN3B gene variants 1210 C/T and 1730 C/T analyzed, no strong association with AD was observed. Conclusion: These observations suggest that the genetic variation of the NR3A, but not NR3B, subunit of the NMDA receptor may be a risk factor for AD pathogenesis among the Taiwanese population.
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GluN3A variants may confer elevated risk of AD onset.
“Additionally, frequency of the Ht2-AG haplotype in the GluN3A gene is higher in AD patients, indicating that GluN3A variants may confer elevated risk of AD onset [59].”
From Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease (2020) · cites this paper as [59]
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- Authors
- Liu, H.-P., Lin, W.-Y., Liu, S.-H., Wang, W.-F., Tsai, C.-H., Wu, B.-T., Wang, C.-K., & Tsai, F.-J.
- Affiliations
- Asia University (TW)
- Changhua Christian Hospital (TW)
- China Medical University Hospital (TW)
- Venue
- Dementia and Geriatric Cognitive Disorders
- Publisher
- S. Karger AG
- Published
- 2009
- Volume
- 28
- Issue
- 6
- Pages
- 521-527
- ISSN
- 1420-8008 (ISSN-L)
- 1421-9824
- OpenAlex
- W2081603018
- Cited by
- 29
- References
- 49
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 2 · 2023: 1 · 2022: 3 · 2021: 4 · 2020: 2 · 2018: 1 · 2016: 3 · 2015: 1 · 2014: 2 · 2012: 3
- FWCI
- 1.33
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Dementia and Geriatric Cognitive Disorders (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- Alzheimer's disease, NMDA receptor, GRIN3A, single nucleotide polymorphisms, genetic susceptibility, haplotypes, memantine, glutamatergic neurotransmission, Taiwanese population
- MeSH terms
- Aged, Alleles, Alzheimer Disease, DNA, Female, Genetic Markers, Genotype, Humans, Male, Middle Aged, Risk Factors, Taiwan, Odds Ratio, Receptors, N-Methyl-D-Aspartate, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide
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