Analysis of BDNF Val66Met allele-specific mRNA levels in bipolar disorder

被引:10
作者
De Luca, Vincenzo [1 ,2 ]
Strauss, John [1 ,2 ]
Semeralul, Mawahib [1 ]
Huang, Sheeda [1 ]
Li, Peter P. [1 ,2 ,3 ]
Warsh, Jerry J. [1 ,2 ,3 ,4 ]
Kennedy, James L. [1 ,2 ,4 ]
Wong, Albert H. C. [1 ,2 ,3 ,4 ]
机构
[1] Ctr Addict & Mental Hlth, Toronto, ON M5T 1R8, Canada
[2] Univ Toronto, Dept Psychiat, Toronto, ON M5S 1A1, Canada
[3] Univ Toronto, Dept Pharmacol, Toronto, ON M5S 1A1, Canada
[4] Univ Toronto, Inst Med Sci, Toronto, ON M5S 1A1, Canada
关键词
neurotrophic factor; bipolar disorder; allelic ratio; parent-of-origin effect; imprinting; intraneuronal trafficking;
D O I
10.1016/j.neulet.2008.06.025
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
We have previously reported an association between the BDNF Val66Met polymorphism and bipolar disorder (BD). However, the possibility that genomic imprinting in BDNF gene affects risk for BD has not been investigated. To examine the possibility of genomic imprinting in the BDNF gene in BD, we analyzed the parent-of-origin effect (POE) and differential expression of the BDNF Val66Met alleles in BD. We performed a family-based association study and ETDT analyses of the Va166Met polymorphism in 312 BD nuclear families, and compared allele-specific mRNA levels in both post-mortem brain samples and B lymphoblasts from BD patients and controls. The BDNF Val66 allele was transmitted significantly more often to patients with BD (maternal transmissions: 46/22, p = 0.003; paternal transmissions: 55/30, p = 0.006). There was no significant difference between maternal and paternal transmission ratios. There was no significant difference in the ratio of Val/Met-specific mRNA expression between BD and controls, in either brain or B lymphoblasts. The Val/Met ratio was much lower in the brain vs. B lymphoblasts. These data do not support a role for genomic imprinting as a modifier of the contribution of BDNF gene to risk of susceptibility to BD. (C) 2008 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:229 / 232
页数:4
相关论文
共 22 条
[1]   Cell-type-specific epigenetic marking of the IL2 gene at a distal cis-regulatory region in competent, nontranscribing T-cells [J].
Adachi, S ;
Rothenberg, EV .
NUCLEIC ACIDS RESEARCH, 2005, 33 (10) :3200-3210
[2]   Cis-acting variation in the expression of a high proportion of genes in human brain [J].
Bray, NJ ;
Buckland, PR ;
Owen, MJ ;
O'Donovan, MC .
HUMAN GENETICS, 2003, 113 (02) :149-153
[3]   Genetics of affective (mood) disorders [J].
Craddock, Nick ;
Forty, Liz .
EUROPEAN JOURNAL OF HUMAN GENETICS, 2006, 14 (06) :660-668
[4]   Regional expression of brain derived neurotrophic factor (BDNF) is correlated with dynamic patterns of promoter methylation in the developing mouse forebrain [J].
Dennis, KE ;
Levitt, P .
MOLECULAR BRAIN RESEARCH, 2005, 140 (1-2) :1-9
[5]   Pedigree disequilibrium tests for multilocus haplotypes [J].
Dudbridge, F .
GENETIC EPIDEMIOLOGY, 2003, 25 (02) :115-121
[6]   Brain-derived neurotrophic factor and neurotrophin 3 in schizophrenic psychoses [J].
Durany, N ;
Michel, T ;
Zöchling, R ;
Boissl, KW ;
Cruz-Sánchez, FF ;
Riederer, P ;
Thome, J .
SCHIZOPHRENIA RESEARCH, 2001, 52 (1-2) :79-86
[7]   The BDNF val66met polymorphism affects activity-dependent secretion of BDNF and human memory and hippocampal function [J].
Egan, MF ;
Kojima, M ;
Callicott, JH ;
Goldberg, TE ;
Kolachana, BS ;
Bertolino, A ;
Zaitsev, E ;
Gold, B ;
Goldman, D ;
Dean, M ;
Lu, B ;
Weinberger, DR .
CELL, 2003, 112 (02) :257-269
[8]  
Emamghoreishi M, 1997, AM J PSYCHIAT, V154, P976
[9]  
Gershon ES, 1996, AM J MED GENET, V67, P202, DOI 10.1002/(SICI)1096-8628(19960409)67:2<202::AID-AJMG11>3.0.CO
[10]  
2-N