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Title: Genetic Variation in n-methyl-d-aspartate Receptor Subunit nr3A but Not nr3b influences Susceptibility to Alzheimer's Disease Source


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Author(s): Liu, HP (Liu, Hsin-Ping); Lin, WY (Lin, Wei-Yong); Liu, SH (Liu, Shu-Hsiang); Wang, WF (Wang, Wen-Fu); Tsai, CH (Tsai, Chon-Haw); Wu, BT (Wu, Bor-Tsang); Wang, CK (Wang, Chien-Kuo); Tsai, FJ (Tsai, Fuu-Jen)

Title: Genetic Variation in N-Methyl-D-Aspartate Receptor Subunit NR3A but Not NR3B Influences Susceptibility to Alzheimer's Disease

Source: DEMENTIA AND GERIATRIC COGNITIVE DISORDERS, 28 (6): 521-527 2009

Language: English

Document Type: Article

Author Keywords: Alzheimer's disease; NMDA receptor; Polymorphism

KeyWords Plus: NR3A-CONTAINING NMDA RECEPTORS; AMYLOID PRECURSOR PROTEIN; LONG-TERM POTENTIATION; SYNAPTIC PLASTICITY; TRANSGENIC MICE; HAPLOTYPE RECONSTRUCTION; REGIONAL EXPRESSION; SURFACE EXPRESSION; CORE PROTEIN; IN-VIVO

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. Copyright (C) 2009 S. Karger AG, Basel

Addresses: [Lin, Wei-Yong; Tsai, Fuu-Jen] China Med Univ Hosp, Dept Med Res, Taichung 404, Taiwan; [Tsai, Chon-Haw] China Med Univ Hosp, Dept Neurol, Taichung 404, Taiwan; [Liu, Shu-Hsiang; Wang, Chien-Kuo; Tsai, Fuu-Jen] Asia Univ, Dept Biotechnol, Taichung, Taiwan; [Wang, Wen-Fu] Chang Hua Christian Hosp, Dept Neurol, Changhua, Taiwan; [Liu, Hsin-Ping] China Med Univ, Grad Inst Acupuncture Sci, Taichung, Taiwan; [Lin, Wei-Yong] China Med Univ, Grad Inst Integrated Med, Taichung, Taiwan; [Tsai, Chon-Haw] China Med Univ, Grad Inst Neural & Cognit Sci, Taichung, Taiwan; [Tsai, Fuu-Jen] China Med Univ, Grad Inst Chinese Med Sci, Taichung, Taiwan; [Wu, Bor-Tsang] China Med Univ, Sch Phys Therapy, Taichung, Taiwan

Reprint Address: Tsai, FJ, China Med Univ Hosp, Dept Med Res, 2 Yuh Der Rd, Taichung 404, Taiwan.

E-mail Address: d0704@www.cmuh.org.tw

Funding Acknowledgement:

Funding Agency

Grant Number

National Science Counsel of Taiwan (NSC) 

97-2320-B-039-019-MY3 

China Medical University 

CMU97-214 




This study was supported by grants from the National Science Counsel of Taiwan (NSC 97-2320-B-039-019-MY3) and China Medical University (CMU97-214).

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Cited Reference Count: 49

Times Cited: 0

Publisher: KARGER

Publisher Address: ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND

ISSN: 1420-8008

DOI: 10.1159/000254757

29-char Source Abbrev.: DEMENT GERIATR COGN DISORD

ISO Source Abbrev.: Dement. Geriatr. Cogn. Disord.

Source Item Page Count: 7

Subject Category: Geriatrics & Gerontology; Clinical Neurology; Psychiatry

ISI Document Delivery No.: 540AN


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