Association Analyses Between Brain-Expressed Fatty-Acid Binding Protein (FABP) Genes and Schizophrenia and Bipolar Disorder
Association Analyses Between Brain-Expressed Fatty-Acid Binding Protein (FABP) Genes and Schizophrenia and Bipolar Disorder
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DOI：
10.1002/ajmg.b.31004
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发表时间：
2010-03-01
影响因子：
2.8
通讯作者：
Yoshikawa, Takeo
中科院分区：
文献类型：
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作者：
Iwayama, Yoshimi;Hattori, Eiji;Yoshikawa, Takeo
前脉冲抑制（PPI）缺陷是精神疾病（如精神分裂症和双相情感障碍）的生物标志物。为了阐明PPI控制机制，我们先前在小鼠中进行了数量性状基因座（QTL）分析，并鉴定了Fabp 7，其编码脑型脂肪酸结合蛋白（Fabp），作为致病基因。在该研究中，人类FABP 7显示出与精神分裂症的遗传关联。FABPs构成一个基因家族，其成员FABP 5和FABP 3也在脑中表达。这些FABP蛋白是多不饱和脂肪酸（PUFA）如花生四烯酸和二十二碳六烯酸的分子伴侣。此外，PUFAs的参与已被记录在精神分裂症和情绪障碍的病理生理学中。因此，在这项研究中，我们研究了FABP 5和3在精神分裂症中的遗传作用（N = 1，900与对照组相结合）以及FABP 7，5和3在双相情感障碍中的遗传作用（N = 1，762病例对照组）。来自FABP 7的三个单核苷酸多态性（SNPs）显示与双相情感障碍存在名义上的相关性，即使在多次测试校正后，同一基因的单倍型也显示与双相情感障碍存在经验性相关性。由于缺乏信息丰富的SNP，我们无法对FABP 5进行关联研究。FABP 3与这两种疾病均无相关性。每个FABP相对较小，并且假定存在控制基因表达的多个调控元件。因此，未来需要鉴定未知的调控元件，以更详细地分析其对精神疾病的遗传贡献。(C)2009威利-利斯公司
Deficits in prepulse inhibition (PPI) are a biological marker for psychiatric illnesses such as schizophrenia and bipolar disorder. To unravel PPI-controlling mechanisms, we previously performed quantitative trait loci (QTL) analysis in mice, and identified Fabp7, that encodes a brain-type fatty acid binding protein (Fabp), as a causative gene. In that study, human FABP7 showed genetic association with schizophrenia. FABPs constitute a gene family, of which members FABP5 and FABP3 are also expressed in the brain. These FABP proteins are molecular chaperons for polyunsaturated fatty acids (PUFAs) such as arachidonic and docosahexaenoic acids. Additionally, the involvement of PUFAs has been documented in the pathophysiology of schizophrenia and mood disorders. Therefore in this study, we examined the genetic roles of FABP5 and 3 in schizophrenia (N = 1,900 in combination with controls) and FABP7, 5, and 3 in bipolar disorder (N = 1,762 in the case-control set). Three single nucleotide polymorphisms (SNPs) from FABP7 showed nominal association with bipolar disorder, and haplotypes of the same gene showed empirical associations with bipolar disorder even after correction of multiple testing. We could not perform association studies on FABP5, due to the lack of informative SNPs. FABP3 displayed no association with either disease. Each FABP is relatively small and it is assumed that there are multiple regulatory elements that control gene expression. Therefore, future identification of unknown regulatory elements will be necessary to make a more detailed analysis of their genetic contribution to mental illnesses. (C) 2009 Wiley-Liss, Inc.