Analysis of BDNF Val66Met allele-specific mRNA levels in bipolar disorder
Analysis of BDNF Val66Met allele-specific mRNA levels in bipolar disorder
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DOI：
10.1016/j.neulet.2008.06.025
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发表时间：
2008-08-22
影响因子：
2.5
通讯作者：
Wong, Albert H. C.
中科院分区：
文献类型：
--
作者：
De Luca, Vincenzo;Strauss, John;Wong, Albert H. C.
我们之前报道过BDNF Val66Met多态性与双相情感障碍（BD）之间的关联。然而，BDNF基因的基因组印迹影响双相障碍风险的可能性尚未得到研究。为了研究BDNF基因基因组印迹的可能性，我们分析了BDNF Val66Met等位基因在BD中的亲子起源效应（POE）和差异表达。我们对312个BD核心家族的Va166Met多态性进行了基于家族的关联研究和ETDT分析，并比较了来自BD患者和对照组的死后脑样本和B淋巴细胞中等位基因特异性mRNA的水平。BDNF Val66等位基因在BD患者中的传播频率明显更高（母体传播：46/22，p = 0.003；父亲传播：55/30，p = 0.006）。母亲和父亲的传播率无显著差异。在脑或B淋巴细胞中，BD与对照组之间Val/ met特异性mRNA表达比例无显著差异。脑中的Val/Met比B淋巴细胞低得多。这些数据不支持基因组印迹作为BDNF基因对双相障碍易感性风险贡献的修饰因子的作用。版权所有。
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.