Genetic variation in N-methyl-D-aspartate receptor subunit NR3A but not NR3B influences susceptibility to Alzheimer's disease.

Bibliographic Collection: 
MOCA Reference, APE
Publication Type: Journal Article
Authors: Liu, Hsin-Ping; Lin, Wei-Yong; Liu, Shu-Hsiang; Wang, Wen-Fu; Tsai, Chon-Haw; Wu, Bor-Tsang; Wang, Chien-Kuo; Tsai, Fuu-Jen
Year of Publication: 2009
Journal: Dement Geriatr Cogn Disord
Volume: 28
Issue: 6
Pagination: 521-7
Publication Language: eng
ISSN: 1421-9824
Keywords: Aged, Alleles, Alzheimer Disease, DNA, Female, Genetic Markers, Genetic Predisposition to Disease, Genotype, Humans, Male, Middle Aged, Odds Ratio, Polymorphism, Single Nucleotide, Receptors, N-Methyl-D-Aspartate, Risk Factors, Taiwan

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.

DOI: 10.1159/000254757
Alternate Journal: Dement Geriatr Cogn Disord