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首页> 外文期刊>Journal of psychiatric research >Analysis of miR-137 expression and rs1625579 in dorsolateral prefrontal cortex
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Analysis of miR-137 expression and rs1625579 in dorsolateral prefrontal cortex

机译：背外侧前额叶皮层miR-137表达及rs1625579分析

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MicroRNAs (miRNAs) are small non-coding RNAs that act as potent regulators of gene expression. A recent GWAS reported the rs1625579 SNP, located downstream of miR-137, as the strongest new association with schizophrenia [Ripke S, Sanders AR, Kendler KS, Levinson DF, Sklar P, Holmans PA, etal. Genome-wide association study identifies five new schizophrenia loci. Nat Genet 2011;43:969-76.]. Prior to this GWAS finding, a schizophrenia imaging-genetic study found miR-137 target genes significantly enriched for association with activation in the dorsolateral prefrontal cortex (DLPFC) [Potkin SG, Macciardi F, Guffanti G, Fallon JH, Wang Q, Turner JA, etal. Identifying gene regulatory networks in schizophrenia. Neuroimage 2010;53:839-47.].We investigated the expression levels of miR-137 and three candidate target genes (ZNF804A, CACNA1C, TCF4) in the DLPFC of postmortem brain tissue from 2 independent cohorts: (1) 26 subjects (10 control (CTR), 7 schizophrenia (SZ), 9 bipolar disorder (BD)) collected at the UCI brain bank; and (2) 99 subjects (33 CTR, 35 SZ, 31 BD) obtained from the Stanley Medical Research Institute (SMRI). MiR-137 expression in the DLPFC did not differ between diagnoses. We also explored the relationship between rs1625579 genotypes and miR-137 expression. Significantly lower miR-137 expression levels were observed in the homozygous TT subjects compared to TG and GG subjects in the control group (30% decrease, p-value=0.03). Moreover, reduced miR-137 levels in TT subjects corresponded to increased levels of the miR-137 target gene TCF4. The miR-137 expression pattern in 9 brain regions was significant for regional effect (ANOVA p-value=1.83E-12), with amygdala and hippocampus having the highest miR-137 expression level. In conclusion, decreased miR-137 expression is associated with the SZ risk allele of rs1625579, and potential regulation of TCF4, another SZ candidate gene. This study offers additional support for involvement of miR-137 and downstream targets as mechanisms of risk for psychiatric disorders.
机译：MicroRNA（miRNA）是小的非编码RNA，可作为有效的基因表达调节剂。最近的GWAS报告说，位于miR-137下游的rs1625579 SNP是与精神分裂症最强的新关联[Ripke S，Sanders AR，Kendler KS，Levinson DF，Sklar P，Holmans PA等。全基因组关联研究确定了五个新的精神分裂症基因座。 Nat Genet 2011; 43：969-76。]。在发现GWAS之前，精神分裂症的成像遗传研究发现miR-137靶基因显着富集，可与背外侧前额叶皮层（DLPFC）中的激活相关联[Potkin SG，Macciardi F，Guffanti G，Fallon JH，Wang Q，Turner JA等。识别精神分裂症的基因调控网络。 Neuroimage 2010; 53：839-47。]。我们调查了来自2个独立队列的死后脑组织DLPFC中miR-137和三个候选靶基因（ZNF804A，CACNA1C，TCF4）的表达水平：（1）26名受试者（在UCI脑库收集了10个对照（CTR），7个精神分裂症（SZ），9个双相情感障碍（BD）; （2）从斯坦利医学研究所（SMRI）获得的99名受试者（33 CTR，35 SZ，31 BD）。诊断之间DLPFC中的MiR-137表达没有差异。我们还探讨了rs1625579基因型与miR-137表达之间的关系。与对照组的TG和GG受试者相比，纯合TT受试者中观察到的miR-137表达水平显着降低（降低30％，p值= 0.03）。而且，TT受试者中miR-137水平降低对应于miR-137靶基因TCF4水平升高。 9个脑区的miR-137表达模式对区域效应具有显着意义（ANOVA p值= 1.83E-12），杏仁核和海马的miR-137表达水平最高。总之，减少的miR-137表达与rs1625579的SZ风险等位基因以及另一种SZ候选基因TCF4的潜在调控有关。这项研究为miR-137和下游靶标作为精神疾病风险的机制提供了额外的支持。

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