脑源性神经营养因子基因多态性与精神分裂症及其认知功能的关联研究
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摘要
目的:探讨脑源性神经营养因子(BDNF)基因多态性与中国汉族精神分裂症(SCZ)发病及其认知功能的关系。方法:对354例SCZ患者(SCZ组)和416名健康对照人群(正常对照组)的BDNF基因4个多态性位点(rs7482257、rs7483883、rs1491850、rs16917234)进行基因分型;采用重复性成套神经心理状态测验(RBANS)对SCZ组及正常对照组进行认知功能评估。结果:SCZ组RBANS注意分、言语分、视觉广度分、即刻记忆分、延迟记忆分及总分明显低于正常对照组(F=1. 40,F=16. 38,F=96. 99,F=41. 12,F=114. 40,F=65. 23; P均<0. 001)。两组BDNF基因4个多态性位点的等位基因(χ2=0. 37～2. 80)、基因型(χ2=1. 06～5. 77)及单体型(χ2=0. 224～2. 979)分布频率比较差异无统计学意义(P均> 0. 05)。在SCZ组中,BDNF基因rs7482257不同基因型间视觉广度因子评分差异有统计学意义(F=3. 79,P=0. 024)。结论:BDNF基因多态性可能与SCZ易感性无关联; BDNF基因rs7482257位点的CC基因型可能与SCZ的视觉广度损害有关。
Objective: To investigate the association of BDNF gene SNP with susceptibility to schizophrenia and cognitive function in patients with schizophrenia in Han Chinese population. Method: Four polymorphisms(rs7482257,rs7483883,rs1491850,rs16917234) of BDNF gene were analyzed in a case-control study,which enrolled 354 schizophrenics(the SCZ group) and 416 healthy control subjects(the control group). We use repeatable battery for the assessment of neuropsychological status(RBANS) to evaluate the cognitive function of 354 schizophrenics and 136 healthy control subjects. Results: The attention score,language score,visuospatial score,immediate score,delayed score and the total score of RBANS of schizophrenics were significantly lower than healthy control subjects(F = 1. 40,P < 0. 001; F = 16. 38,P < 0. 001; F = 96. 99,P < 0. 001; F =41. 12,P < 0. 001; F = 114. 40,P < 0. 001; F = 65. 23,P < 0. 001). The genotype(χ2= 1. 06-5. 77) and allele(χ2= 0. 37-2. 80) frequencies in the four SNPs of BDNF gene between the two groups had no statistically significant differences(all P > 0. 05). The visuospatial score in schizophrenics showed significant differences between different genotypes of rs7482257(F = 3. 79,P = 0. 024). Conclusion: BDNF gene polymorphisms are not associated with schizophrenia in Han Chinese population. The CC genotype of rs7482257 in BDNF gene may be associated with visuospatial impairment of schizophrenia.
Objective: To investigate the association of BDNF gene SNP with susceptibility to schizophrenia and cognitive function in patients with schizophrenia in Han Chinese population. Method: Four polymorphisms(rs7482257,rs7483883,rs1491850,rs16917234) of BDNF gene were analyzed in a case-control study,which enrolled 354 schizophrenics(the SCZ group) and 416 healthy control subjects(the control group). We use repeatable battery for the assessment of neuropsychological status(RBANS) to evaluate the cognitive function of 354 schizophrenics and 136 healthy control subjects. Results: The attention score,language score,visuospatial score,immediate score,delayed score and the total score of RBANS of schizophrenics were significantly lower than healthy control subjects(F = 1. 40,P < 0. 001; F = 16. 38,P < 0. 001; F = 96. 99,P < 0. 001; F =41. 12,P < 0. 001; F = 114. 40,P < 0. 001; F = 65. 23,P < 0. 001). The genotype(χ2= 1. 06-5. 77) and allele(χ2= 0. 37-2. 80) frequencies in the four SNPs of BDNF gene between the two groups had no statistically significant differences(all P > 0. 05). The visuospatial score in schizophrenics showed significant differences between different genotypes of rs7482257(F = 3. 79,P = 0. 024). Conclusion: BDNF gene polymorphisms are not associated with schizophrenia in Han Chinese population. The CC genotype of rs7482257 in BDNF gene may be associated with visuospatial impairment of schizophrenia.
引文
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[15] Terracciano A,Piras MG,Lobina M,et al. Genetics of serum BDNF:meta-analysis of the Val66Met and genome-wide association study[J]. World J Biol Psychiatry,2013,14(8):583-589.
[2] Huang EJ,Reichardt LF. Neurotrophins:roles in neuronal development and function[J]. Annu Rev Neurosci,2001,24(1):677-736.
[3] Schmidt-Kastner R,Van Os J,Wms H,et al. Gene regulation by hypoxia and the neurodevelopmental origin of schizophrenia[J].Schizophr Res,2006,84(2-3):253-271.
[4] Woo NH,Teng HK,Siao CJ,et al. Activation of p75NTR by proBDNF facilitates hippocampal long-term depression[J]. Nat Neurosci,2005,8(8):1069-1077.
[5] Lu B,Gottschalk W. Modulation of hippocampal synaptic transmission and plasticity by neurotrophins[J]. Prog Brain Res,2000,128:231-241.
[6] Lu W,Zhang C,Yi Z,et al. Association between BDNF Val66Met polymorphism and cognitive performance in antipsychotic-naive patients with schizophrenia[J]. J Mol Neurosci,2012,47(3):505-510.
[7] Zhang XY,Chen Da C,Tan YL,et al. BDNF polymorphisms are associated with cognitive performance in schizophrenia patients versus healthy controls[J]. J Clin Psychiatry,2016,77(8):1011-1018.
[8] Collins AL,Kim Y,Sklar P,et al. Hypothesis-driven candidate genes for schizophrenia compared to genome-wide association results[J]. Psychol Med,2012,42(3):607-616.
[9] Gallhofer B,Bauer U,Lis S,et al. Cognitive dysfunction in schizophrenia:comparison of treatment with atypical antipsychotic agents and conventional neuroleptic drugs[J]. Eur Neuropsychopharmacol,1996,6(2):13-20.
[10] Egan MF,Kojima M,Callicott JH,et al. The BDNF val66met polymorphism affects activity-dependent secretion of BDNF and human memory and hippocampal function[J]. Cell,2003,112(2):257-269.
[11] Ho BC,Milev P,O'leary DS,et al. Cognitive and magnetic resonance imaging brain morphometric correlates of brain-derived neurotrophic factor Val66Met gene polymorphism in patients with schizophrenia and healthy volunteers[J]. Arch Gen Psychiatry,2006,63(7):731-740.
[12] Zhang XY,Chen DC,Xiu MH,et al. Cognitive and serum BDNF correlates of BDNF Val66Met gene polymorphism in patients with schizophrenia and normal controls[J]. Hum Genet,2012,131(7):1187-1195.
[13] Mohamed S,Paulsen JS,O'leary D,et al. Generalized cognitive deficits in schizophrenia:a study of first-episode patients[J].Arch Gen Psychiatry,1999,56(8):749-754.
[14] Park S,Holzman PS. Schizophrenics show spatial working memory deficits[J]. Arch Gen Psychiatry,1992,49(12):975-982.
[15] Terracciano A,Piras MG,Lobina M,et al. Genetics of serum BDNF:meta-analysis of the Val66Met and genome-wide association study[J]. World J Biol Psychiatry,2013,14(8):583-589.