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Ethanol treatment of lymphoblastoid cell lines from alcoholics and non-alcoholics causes many subtle changes in gene expression

机译:酒精处理酒精中毒者和非酒精中毒的淋巴母细胞细胞系会引起基因表达的许多细微变化

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摘要

To elucidate the effects of a controlled exposure to ethanol on gene expression, we studied lymphoblastoid cell lines (LCLs) from 21 alcoholics and 21 controls. We cultured each cell line for 24h with and without 75mM ethanol and measured gene expression using microarrays. Differences in expression between LCLs from alcoholics and controls included 13 genes previously identified as associated with alcoholism or related traits, including KCNA3, DICER1, ZNF415, CAT, SLC9A9, and PPARGC1B. The paired design allowed us to detect very small changes due to ethanol treatment: ethanol altered the expression of 37% of the probe sets (51% of the unique named genes) expressed in these LCLs, most by modest amounts. Ninety-nine percent of the named genes expressed in the LCLs were also expressed in brain. Key pathways affected by ethanol include cytokine, TNF, and NFκB signaling. Among the genes affected by ethanol were ANK3, EPHB1, SLC1A1, SLC9A9, NRD1, and SH3BP5, which were reported to be associated with alcoholism or related phenotypes in 2 genome-wide association studies. Genes that either differed in expression between alcoholics and controls or were affected by ethanol exposure are candidates for further study.
机译:为了阐明受控暴露于乙醇对基因表达的影响,我们研究了来自21个酗酒者和21个对照的淋巴母细胞样细胞系(LCL)。我们在有和没有75mM乙醇的情况下将每个细胞系培养24小时,并使用微阵列测量基因表达。来自酗酒者和对照组的LCL之间的表达差异包括13个先前被确定与酗酒或相关性状相关的基因,包括KCNA3,DICER1,ZNF415,CAT,SLC9A9和PPARGC1B。配对设计使我们能够检测到由于乙醇处理而引起的很小的变化:乙醇改变了这些LCL中37%的探针集(唯一命名基因的51%)的表达,但变化幅度不大。在LCL中表达的99%的命名基因也在大脑中表达。受乙醇影响的关键途径包括细胞因子,TNF和NFκB信号传导。在受到乙醇影响的基因中,有ANK3,EPHB1,SLC1A1,SLC9A9,NRD1和SH3BP5,它们在2个全基因组关联研究中均与酒精中毒或相关表型有关。酗酒者与对照组之间的表达差异较大或受到乙醇暴露影响的基因有待进一步研究。

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