Genetic variability in the NMDA-dependent AMPA trafficking cascade is associated with alcohol dependence.
Genetic variability in the NMDA-dependent AMPA trafficking cascade is associated with alcohol dependence.
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DOI：
10.1111/j.1369-1600.2011.00338.x
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发表时间：
2012-07
影响因子：
3.4
通讯作者：
Biernacka JM
中科院分区：
文献类型：
--
作者：
Karpyak VM;Geske JR;Colby CL;Mrazek DA;Biernacka JM
小鼠模型研究表明，酒精戒断的严重程度与MPDZ基因的多态性变异和表达相关。目前关于人类MPDZ基因变异的知识是有限的，然而，我们的数据表明它与酒精依赖的潜在关联。MPDZ蛋白是NMDA依赖性AMPA受体运输级联的重要组成部分，其控制谷氨酸相关兴奋性神经传递。为了研究依赖NMDA的AMPA运输级联中的变异与酒精依赖的关联，我们使用成瘾研究：遗传与环境（SAGE）的单核苷酸多态性（SNP）数据进行了基因集（途径）分析。基因集分析不是单独地测试与每个SNP的关联，其通常具有检测多个SNP的小影响的低能力，而是应用单个统计测试来评估一组基因中的变异是否与感兴趣的表型相关。对该通路中13个基因的988个SNP的基因集分析表明，该通路中变异的总体效应与酒精依赖显著相关，p<0.01。酒精依赖与NMDA依赖性AMPA受体转运级联中遗传变异的统计学显著相关性表明需要进一步研究该途径在酒精依赖中的作用。
Model studies in mice indicate that the severity of alcohol withdrawal is associated with polymorphic variation and expression of the MPDZ gene. Current knowledge about variation in the human MPDZ gene is limited; however, our data indicate its potential association with alcohol dependence. The MPDZ protein is an important part of the NMDA-dependent AMPA receptor trafficking cascade that controls glutamate-related excitatory neurotransmission. To investigate association of variation in the NMDA-dependent AMPA trafficking cascade with alcohol dependence, we performed a gene-set (pathway) analysis using single nucleotide polymorphism (SNP) data from the Study of Addiction: Genetic and Environment (SAGE). Rather than testing for association with each SNP individually, which typically has low power to detect small effects of multiple SNPs, gene set analysis applies a single statistical test to evaluate whether variation in a set of genes is associated with the phenotype of interest. Gene-set analysis of 988 SNPs in 13 genes in the pathway demonstrated a significant association with alcohol dependence, with p<0.01 for the global effect of variation in this pathway. The statistically significant association of alcohol dependence with genetic variation in the NMDA-dependent AMPA receptor trafficking cascade indicates a need for further investigation of the role of this pathway in alcohol dependence.
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DOI：
10.1111/j.1530-0277.2008.00888.x
发表时间：
2009-04
期刊：
Alcoholism, clinical and experimental research
影响因子：
--
作者：
Karpyak VM;Kim JH;Biernacka JM;Wieben ED;Mrazek DA;Black JL;Choi DS
通讯作者：
Choi DS
影响因子：
2.9
作者：
BREESE, CR;FREEDMAN, R;LEONARD, SS
通讯作者：
LEONARD, SS
影响因子：
2.1
作者：
Gauderman, W. James;Murcray, Cassandra;Conti, David V.
通讯作者：
Conti, David V.
DOI：
10.1111/j.1530-0277.2007.00344.x
发表时间：
2007-04-01
影响因子：
3.2
作者：
Krupitsky, Evgeny M.;Rudenko, Anatoly A.;Krystal, John H.
通讯作者：
Krystal, John H.
DOI：
10.1111/j.1530-0277.2010.01156.x
发表时间：
2010-05
期刊：
Alcoholism, clinical and experimental research
影响因子：
--
作者：
Edenberg HJ;Koller DL;Xuei X;Wetherill L;McClintick JN;Almasy L;Bierut LJ;Bucholz KK;Goate A;Aliev F;Dick D;Hesselbrock V;Hinrichs A;Kramer J;Kuperman S;Nurnberger JI Jr;Rice JP;Schuckit MA;Taylor R;Todd Webb B;Tischfield JA;Porjesz B;Foroud T
通讯作者：
Foroud T