散发性阿尔茨海默病患者BDNF基因G196A和C270T单体型及双体型分析-东南大学学报医学版

散发性阿尔茨海默病患者BDNF基因G196A和C270T单体型及双体型分析

单位：东南大学附属中大医院,神经内科,江苏,南京,210009

分类号：R749.16, Q75

出版年·卷·期（页码）：2008·27·第三期（161-165）

摘要：

目的:探讨脑源性神经营养因子(BDNF)基因G196A和C270T单核苷酸多态性(SNPs)在散发性阿尔茨海默病(sAD)发病机制中的作用.方法:采用聚合酶链反应限制性片段长度多态性(PCR-RFLP)技术,对105例sAD患者和105例健康对照者BDNF基因、载脂蛋白E(ApoE)基因多态性进行分析.结果:(1)sAD患者C270T但非G196A基因型及等位基因频率与对照组相比差异有统计学意义(P=0.034,P=0.011).(2)BDNF G196A和C270T单体型分析发现,4种单体型在sAD组和对照组间差异有统计学意义(P=0.048).对照组H4单体型频率显著高于sAD组,差异有统计学意义(P=0.024);按ApoEε4分层后,在非ApoEε4携带者中,该差异仍有统计学意义(P=0.023).对照组基于H4的双体型频率显著高于sAD组,差异有统计学意义(P=0.029);按ApoEε4分层后,在非ApoEε4携带者中,该差异仍有统计学意义(P=0.040).结论:BDNF C270T 位点的SNP可能与sAD的易感性相关,H4单体型及其构成的双体型是sAD的遗传保护因素,对非ApoEε4携带者而言尤其如此.

Objective To explore the association between brain-derived neurotrophic factor(BDNF) gene and ApoE gene polymorphisms and sporadic Alzheimer disease(sAD).Methods The polymorphisms of BDNF G196A,C270T and ApoE gene were determined in 105 sAD and 105 controls by polymerase chain reaction-restriction fragment length polymorphism method.Results(1)No significant differences in the distributions of BDNF G196A polymorphisms were found between sAD and controls(χ2=0.338,P=0.844).Significant differences in the distributions of ApoE and BDNF C270T polymorphisms were found between sAD and controls(χ2=32.586,P=0.000,χ2=6.764,P=0.034,respectively).(2)The distribution of frequencies of 4 haplotypes showed a significant difference(χ2=7.890,P=0.048).The haplotype frequency of H4 were remarkably higher in controls than in sAD.Stratification of the data according to the ApoE status showed that in non-ApoEε4 allele carriers there was a significant difference in the frequency of H4 haplotype(P=0.023).(3)Diplotype with the H4 haplotype was also remarkably higher in controls than in sAD.Stratification of the data according to the ApoE status showed that in ApoEε4 allele bearers there was no significant difference in the frequency of diplotype with the H4 haplotype,although there was a significant difference between the two groups in non-ApoEε4 carriers(P=0.040).ConclusionBDNF genetic variation may possibly affect the risk for sAD,particularly in subjects who are ApoEε4 negative.

参考文献：

[1] GATZ M, PEDERSEN N L, BERG S. Heritability for Alzheimer's disease:the study of dementia in Swedish twins, 1997
[2] BLENNOW K, de LEON M J, ZETTERBERG H. Alzheimer's disease. 2006(9533). doi:10.1016/S0140-6736(6)69113-7
[3] PHILLIPS H S, HAINS J M, ARMANINI M. BDNF mRNA is decreased in the hippocampus of individuals with Alzheimer's disease. 1991. doi:10.1016/0896-6273(91)90273-3
[4] EGAN M F, KOJIMA M, CALLICOTT J H. The BDNF val66met polymorphism affects activity-dependent secretion of BDNF and human memory and hippocampal function. 2003. doi:10.1016/S0092-8674(3)00035-7
[5] KUNUGI H, UEKI A, OTSUKA M. A novel polymorphism of the brain derived neurotrophic factor (BDNF) gene associated with late-onset Alzheimer's disease. 2001. doi:10.1038/sj.mp.4000792
[6] TSAI S J, HONG C J, LIU H C. Association analysis of brain-derived neurotrophic factor Val66Met polymorphisms with Alzheimer's disease and age of onset. 2004. doi:10.1159/000075332
[7] 赵书平, 张俊洁, 尤建. 一种碘化钾提取外周血基因组DNA的方法. 中华医学遗传学杂志1999(6)
[8] WENHAM P R, PRICE W H, BLANDELL G. Apolipoprotein E genotyping by one-stage PCR, 1991
[9] SHI Y Y, HE L. SHEsis,a powerful software platform for analyses of linkage disequilibrium,haplotype construction,and genetic association at polymorphism loci. 2005(3). doi:10.1038/sj.cr.7290286
[10] MURER M G, YAN Q, RAISMAN-VOZARI R. Brain-derived neurotrophic factor in the control human brain,and in Alzheimer's disease and Parkinson's disease. 2001. doi:10.1016/S0301-0082(0)00014-9
[11] INGELSSON M, HYMAN B T. Disordered proteins in dementia. 2002(4). doi:10.1080/078538902320322529
[12] BIAN J T, ZHANG J W, ZHANG Z X. Association analysis of brain-derived neurotrophic factor(BDNF)gene 196A/G polymorphism with Alzheimer's disease (AD) in mainland Chinese. 2005. doi:10.1016/j.neulet.2005.07.009
[13] HE X M, ZHANG Z X, ZHANG J W. Lack of association between the BDNF gene Val66Met polymorphism and Alzheimer disease in a Chinese Han population. 2007(3/4). doi:10.1159/000106473
[14] TSAI S J, HONG C J, LIU H C. The brain-derived neurotrophic factor gene as a possible susceptibility candidate for Alzheimer's disease in a Chinese population. 2006. doi:10.1159/000090673
[15] DESAI P, NEBES R, DEKOSKY S T. Investigation of the effect of brain-derived neurotrophic factor (BDNF) polymorphisms on the risk of late-onset Alzheimer's disease (AD) and quantitative measures of AD progression. 2005. doi:10.1016/j.neulet.2005.01.008
[16] HUANG Y. Apolipoprotein E and Alzheimer disease. 2006(z1). doi:10.1212/01.wnl.0000192102.41141.9e
[17] 林洁, 刘景晶, 陈庆梅. 抗阿尔茨海默病重组蛋白疫苗的克隆、表达和免疫学鉴定. 东南大学学报(医学版)2006(4). doi:10.3969/j.issn.1671-6264.2006.04.003

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