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

• Published in: Dementia and geriatric cognitive disorders 2009-01, Vol.28 (6), p.521-527
• Main 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
• Format: Article
• Language: English
• Subjects: Aged; Alleles; Alzheimer Disease - epidemiology; Alzheimer Disease - genetics; Alzheimer Disease - psychology; Biological and medical sciences; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; DNA - genetics; Female; Genetic Markers; Genetic Predisposition to Disease - epidemiology; Genetic Predisposition to Disease - genetics; Genetic Predisposition to Disease - psychology; Genotype; Humans; Male; Medical sciences; Middle Aged; Neurology; Neuropharmacology; Neuroprotective agent; Odds Ratio; Original Research Article; Pharmacology. Drug treatments; Polymorphism, Single Nucleotide - genetics; Receptors, N-Methyl-D-Aspartate - genetics; Risk Factors; Taiwan - epidemiology
• ISSN: 1420-8008; 1421-9824
• DOI: 10.1159/000254757

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.