| 1 | J. Hum. Genet. 2010 Feb 55: 127-30 |
|---|---|
| PMID | 20057506 |
| Title | Polymorphism screening of brain-expressed FABP7, 5 and 3 genes and association studies in autism and schizophrenia in Japanese subjects. |
| Abstract | 脂肪酸结合蛋白(FABP)基因全家ly encode fatty acid-binding proteins and consist of at least 12 members, of which FABP7, 5 and 3 are expressed in the brain. We previously showed that FABP7 is associated withschizophreniaand bipolar disorder. Recently, genetic overlap between autism andschizophreniahas been reported. Therefore, in this study, we set out to examine the possible roles of brain-expressed FABPs in autism, focusing primarily on potentially functional polymorphisms (that is, missense polymorphisms). First, we resequenced the three genes using 285 autism samples. We identified 13 polymorphisms, of which 7 are novel. Of the novel single-nucleotide polymorphisms (SNPs), two are missense mutations, namely, 376G>C (Val126Leu) in FABP7 and 340G>C (Gly114Arg) inFABP5. Second, we tested for the genetic association of four missense SNPs with autism andschizophrenia, but failed to detect significant results. Finally, as a web-based algorithm predicts that the 8A>G (Asp3Gly; rs17848124) in FABP3 is 'probably damaging', we estimated the possible impact of this SNP, and found that the loss of charge and salt bridge, caused by the Asp3-to-Gly3, may affect stability of the FABP3 protein. Future searches for associated phenotypes with missense SNPs using larger samples are highly warranted. |
| SCZ Keywords | schizophrenia |
| 2 | 点。j .地中海,麝猫。B Neuropsychiatr。基因t. 2010 Mar 153B: 484-93 |
| PMID | 19554614 |
| Title | Association analyses between brain-expressed fatty-acid binding protein (FABP) genes and schizophrenia and bipolar disorder. |
| Abstract | Deficits in prepulse inhibition (PPI) are a biological marker for psychiatric illnesses such asschizophreniaand 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 withschizophrenia. FABPs constitute a gene family, of which membersFABP5and 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 ofschizophreniaand mood disorders. Therefore in this study, we examined the genetic roles ofFABP5and 3 inschizophrenia(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 onFABP5, 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. |
| SCZ Keywords | schizophrenia |
| 3 | Hum. Mol. Genet. 2014 Dec 23: 6495-511 |
| PMID | 25027319 |
| Title | Functional characterization of FABP3, 5 and 7 gene variants identified in schizophrenia and autism spectrum disorder and mouse behavioral studies. |
| Abstract | Disturbances of lipid metabolism have been implicated in psychiatric illnesses. We previously reported an association between the gene for fatty acid binding protein 7 (FABP7) andschizophrenia. Furthermore, we identified and reported several rare non-synonymous polymorphisms of the brain-expressed genes FABP3,FABP5and FABP7 fromschizophreniaand autism spectrum disorder (ASD), diseases known to part share genetic architecture. Here, we conducted further studies to better understand the contribution these genes make to the pathogenesis ofschizophreniaand ASD. In postmortem brains, we detected altered mRNA expression levels ofFABP5inschizophrenia, and of FABP7 in ASD and alteredFABP5in peripheral lymphocytes. Using a patient cohort, comprehensive mutation screening identified six missense and two frameshift variants from the three FABP genes. The two frameshift proteins, FABP3 E132fs and FABP7 N80fs, formed cellular aggregates and were unstable when expressed in cultured cells. The four missense mutants with predicted possible damaging outcomes showed no changes in intracellular localization. Examining ligand binding properties, FABP7 S86G and FABP7 V126L lost their preference for docosahexaenoic acid to linoleic acid. Finally, mice deficient in Fabp3,FABP5and Fabp7 were evaluated in a systematic behavioral test battery. The Fabp3 knockout (KO) mice showed decreased social memory and novelty seeking, and Fabp7 KO mice displayed hyperactive and anxiety-related phenotypes, whileFABP5KO mice showed no apparent phenotypes. In conclusion, disturbances in brain-expressed FABPs could represent an underlying disease mechanism in a proportion ofschizophreniaand ASD sufferers. |
| SCZ Keywords | schizophrenia |
| 4 | Neurosci. Res. 2016 Jan 102: 47-55 |
| PMID | 25205626 |
| Title | Fatty acid binding proteins and the nervous system: Their impact on mental conditions. |
| Abstract | The brain is rich in lipid and fatty molecules. In this review article, we focus on fatty acid binding proteins (Fabps) that bind to fatty acids such as arachidonic acid and docosahexianoic acid and transfer these lipid ligands within the cytoplasm. Among Fabp family molecules, Fabp3,FABP5, and Fabp7 are specifically localized in neural stem/progenitor cells, neurons and glia in a cell-type specific manner. Quantitative trait locus analysis has revealed that Fabp7 is related with performance of prepulse inhibition (PPI) that is used as an endophenotype of psychiatric diseases such asschizophrenia.FABP5and Fabp7 play important roles on neurogenesis and differentially regulate acoustic startle response and PPI. However, other behavior performances including spatial memory, anxiety-like behavior, and diurnal changes in general activity were not different in mice deficient for Fabp7 orFABP5. Considering the importance of fatty acids in neurogenesis, we would like to emphasize that lipid nutrition and its dynamism via Fabps play significant roles in mental conditions. This might provide a good example of how nutritional environment can affect psychiatric conditions at the molecular level. |
| SCZ Keywords | schizophrenia |