Abstract
Objective
N-methyl-D-aspartate (NMDA) receptor has been indicated to be involved in the pathogenesis of Alzheimer’s disease (AD). The NMDA receptor subunit 2b (NR2B) has attracted more attention due to its characteristic distribution and selective reduction in AD brain. The present study aimed to explore the association between NMDA gene polymorphism and AD.
Methods
A total of 63 AD patients and 68 normal controls in Shanghai city were employed in this study. Genotype of C2664T variant (rs1806201) in the exon13 of GRIN2B gene was determined by gene sequencing.
Results
Among AD patients, 15 (23.6%) subjects were identified as C/C genotype, and 35 (55.6%) were identified as C/T genotype. The left 13 (20.6%) subjects were identified as T/T genotype. In normal controls, 15 (22.1%) subjects were identified as C/C genotype, 39 (57.4%) as C/T genotype and 14 (20.6%) as T/T genotype. The distribution frequency of neither GRIN2B C2664T genotype (P=0.895) nor allele (P=0.790) was significantly different between AD patients and normal controls, even when the subjects were stratified by gender and age of disease onset in AD patients.
Conclusion
The results suggest that there is no relation between GRIN2B C2664T polymorphism and AD in Chinese Han population of Shanghai City.
摘要
目的
N-甲基-D-天冬氨酸(N-methyl-D-aspartate, NMDA)受体功能异常可能与阿尔茨海默病(Alzheimer’s disease, AD)的发病有关。 NMDA的NR2B 亚基由于在中枢神经具有特定的分布规律, 并被发现在AD的脑组织中选择性表达下降, 因而备受关注。 本研究旨在探讨NMDA受体NR2B 亚基基因(GRIN2B) C2664T 多态性与上海地区汉族人群阿尔茨海默病的关系。
方法
在63 例AD患者和68 例对照者中, 采用基因测序法对GRIN2B基因第13个外显子区的C2664T单核苷酸多态性(rs180620)进行检测, 在等位基因和基因型水平上进行比较。
结果
AD组中有15 名患者基因型为C/C (23.6%), 35 名基因型为C/T (55.6%), 13 名为T/T (20.6%)。 在健康对照组中, C/C、 C/T 和T/T 基因型的人数分别为15 (22.1%)、 39 (57.4%)和14 (20.6%)。 在基因型和等位基因水平, NR2B 亚基基因多态性均未显示出与AD 的相关性。 得到的数据经性别和发病年龄分层比较后, 仍未显示出相关性。
结论
GRIN2B基因C2664T 多态性与上海地区汉族人群罹患AD无相关性。
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References
Zhang MY, Yu X, Xiao SF. Manual for Prevention and Treatment of Geriatric Dementia. Peking University’s Medical Press 2007: 4.
Okouchi M, Ekshyyan O, Maracine M, Aw TY. Neuronal apoptosis in neurodegeneration. Antioxid Redox Signal 2007, 9: 1059–1096.
Kalia LV, Kalia SK, Salter MW. NMDA receptors in clinical neurology: excitatory times ahead. Lancet Neurol 2008, 7: 742–755.
Lau CG, Zukin RS. NMDA receptor trafficking in synaptic plasticity and neuropsychiatric disorders. Nat Rev Neurosci 2007, 8: 413–426.
Alberdi E, Sánchez-Gómez MV, Cavaliere F, Pérez-Samartín A, Zugaza JL, Trullas R, et al. Amyloid beta oligomers induce Ca2+ dysregulation andneuronal death through activation of ionotropic glutamate receptors. Cell Calcium 2010, 47: 264–272.
Hallett PJ, Standaert DG. Rationale for and use of NMDA receptor antagonists in Parkinson’s disease. Pharmacol Ther 2004, 102: 155–174.
Fan MM, Raymond LA. N-methyl-D-aspartate (NMDA) receptor function and excitotoxicity in Huntington’s disease. Prog Neurobiol 2007, 81: 272–293.
Fuller PI, Reddrop C, Rodger J, Bellingham MC, Philips JK. Differential expression of NMDA 2B receptor subunit in motoneuron populations susceptible and resistant to amyotrophic lateral sclerosis. Neurosci Lett 2006, 399: 157–161.
Monyer H, Sprengel R, Schoepfer R, Herb A, Higuchi M, Lomeli H, et al. Heteromeric NMDA receptors: Molecular and function distinction of subtypes. Science 1992, 256: 1217–1221.
Sun L, Shipley MT, Lidow MS. Expression of NR1, NR2A-D, and NR3 subuints of the NMDA receptor in the cerebral cortex and olfactory bulb of adult rat. Synapse 2000, 35: 212–221.
Hynd MR, Scott HL, Dodd PR. Differential expression of the Nmethyl-D-aspartate receptor NR2 isoforms in Alzheimer’s disease. J Neurochem 2004, 90: 913–919.
Hu NW, Klyubin I, Anwy R, Rowan MJ. GluN2B subunit-containing NMDA receptor antagonists prevent Abeta-mediated synaptic plasticity disruption in vivo. Pro Natl Acad Sci U S A 2009, 106: 20504–20509.
Tang YP, Sinizu E, Dube GR, Dube GR, Rampon C, Kerchner GA, et al. Genetic enhancement of learning and memory in mice. Nature 1999, 401: 63–69.
Clayton DA, Mesches MH, Alvarez E, Bichford PC, Browning MD. A hippocampal NR2B deficit can mimic age-related changes in long-term potentiation and spatial learning in the Fischer 344 rat. J Neurosci 2002, 22: 3628–3637.
Mandich P, Schito AM, Bellone E, Antonacci R, Finelli P, Rocchi M, et al. Mapping of the human NMDAR2B receptor subunit gene (GRIN2B) to chromosome 12p12. Genomics 1994, 22: 216–218.
Di Maria E, Gulli R, Begni S, De Luca A, Bignotti S, Pasini A, et al. Variations in the NMDA receptor subunit 2B gene (GRIN2B) and schizophrenia. Am J Med Genet 2004, 128: 27–29.
Tsai SJ, Liu HC, Liu TY, Cheng CY, Hong CJ. Association analysis for genetic variants of NMDA receptor 2b subunit (GRIN2B) and Parkinson’s disease. J Neural Transm 2002, 109: 483–488.
Arning L, Saft C, Wieczorek S, Andrich J, Kraus PH, Epplen JT. NR2A and NR2B receptor gene variations modify age at onset in Huntington disease in a sex-specific manner. Hum Genet 2007, 122: 175–182.
McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM. Clinical diagnosis of Alzheimer’s disease: report of the NINCDS-ADRDA work group under the auspices of Department of Health and Human Services Task Force on Alzheimer’s disease. Neurology 1984, 11: 939–944.
Folstein MF, Folstein SE, McHugh PR. “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. J Psychiat Res 1975, 12: 189–198.
Miyoshi K. What is ‘early onset dementia’? Psychogeriatrics 2009, 9: 67–72.
Seripa D, Matera MG, Franceschi M, Bizzarro A, Paris F, Cascavilla L, et al. Association analysis of GRIN2B, encoding Nmethyl-D-aspartate receptor 2B subunit, and Alzheimer’s disease. Dement Geriatr Cogn Disord 2008, 25: 287–292.
Tsai SJ, Liu HC, Liu TY, Cheng CY, Hong CJ. Association analysis for the genetic variants of the NMDA receptor subunit 2b and Alzheimer’s disease. Dement Geriatr Cogn Disord 2002, 13: 91–94.
Nishiguchi N, Shirakawa O, Ono H, Hashimoto T, Maeda K. Novel polymorphism in the gene region encoding the carboxylterminal intracellular domain of the NMDA receptor 2B subunit: Analysis of association with schizophrenia. Am J Psychiatry 2000, 157: 1329–1331.
Wernicke C, Samochowiec J, Schmidt LG, Winterer G, Smolka M, Kucharska-Mazur J, et al. Polymorphisms in the N-methyl-D-aspartate receptor 1 and 2B subunits are associated with Alcoholism-related traits. Biol Psychiatry 2003, 54: 922–928.
Cacabelos R. Influence of pharmacogenetic factors on Alzheimer’s disease therapeutics. Neurodegenerative Dis 2008, 5: 176–178.
Hong CJ, Yu WY, Lin CH, Cheng CY, Tsai SJ. Association analysis for NMDA receptor subunit 2B (GRIN2B) genetic variants and psychopathology and clozapine response in schizophrenia. Psychiatric Genetics 2001, 11: 219–222.
Jiang HQ, Jia JP. Association between NR2B subunit gene (GRIN2B) promoter polymorphisms and sporadic Alzheimer’s disease in the North Chinese population. Neurosci Lett 2009, 450: 356–360.
Reitz C, Mayeux R. Use of genetic variation as biomarkers for Alzheimer’s disease. Ann NY Acad Sci 2009, 1180: 75–96.
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Chen, C., Li, X., Wang, T. et al. Association between NMDA receptor subunit 2b gene polymorphism and Alzheimer’s disease in Chinese Han population in Shanghai. Neurosci. Bull. 26, 395–400 (2010). https://doi.org/10.1007/s12264-010-0729-2
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DOI: https://doi.org/10.1007/s12264-010-0729-2