BioProject

Compared gene expression in lymphoblasoid cell lines from alcholics and controls and 24 hr treatment with ethanol. More...

Compared gene expression in lymphoblasoid cell lines from alcholics and controls and 24 hr treatment with ethanol. 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 24 h with and without 75 mM ethanol and measured gene expression using microarrays. Differences in expression between LCL from alcoholics and controls were modest, but included 13 genes previously identified as associated with alcoholism or related traits in one or more GWAS, including KCNA3, DICER1, ZNF415, Catalase 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) detectably expressed in these LCLs, but most by very modest amounts. 99% of the named genes expressed in the LCLs were also expressed in at least 1 of 9 brain regions tested, suggesting that LCLs are a reasonable and accessible proxy for brain tissues. Key pathways affected by ethanol include cytokine, TNF and NF-kB 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. Overall design: Lymphoblastoid cells from 21 alcoholics and 21 controls were treated with 75mM ethanol for 24 hours. Less...