title: Ethanol treatment of lymphoblastoid cell lines from alcoholics and non-alcoholics causes many subtle changes in gene expression.
abstract: 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 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.
authors.affiliation: Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Jeanette N
authors.initials: JN
authors.lastname: McClintick
authors.affiliation: Department of Genetics and the Human Genetics Institute of New Jersey, Rutgers University, Piscataway, NJ, USA.
authors.forename: Andrew I
authors.initials: AI
authors.lastname: Brooks
authors.affiliation: Department of Genetics and the Human Genetics Institute of New Jersey, Rutgers University, Piscataway, NJ, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Deng
authors.affiliation: Department of Genetics and the Human Genetics Institute of New Jersey, Rutgers University, Piscataway, NJ, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Liang
authors.affiliation: Department of Psychiatry, B8134, Washington University School of Medicine, 660 S. Euclid Ave., St. Louis, MO 63110, USA.
authors.forename: Jen C
authors.initials: JC
authors.lastname: Wang
authors.affiliation: Department of Psychiatry, B8134, Washington University School of Medicine, 660 S. Euclid Ave., St. Louis, MO 63110, USA.
authors.forename: Manav
authors.initials: M
authors.lastname: Kapoor
authors.affiliation: Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Xuei
authors.affiliation: Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Foroud
authors.affiliation: Department of Genetics and the Human Genetics Institute of New Jersey, Rutgers University, Piscataway, NJ, USA.
authors.forename: Jay A
authors.initials: JA
authors.lastname: Tischfield
authors.affiliation: Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN, USA; Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA. Electronic address: edenberg@iu.edu.
authors.forename: Howard J
authors.initials: HJ
authors.lastname: Edenberg
mesh_terms: D000437:Alcoholism / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D000431:Ethanol / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D055106:Genome-Wide Association Study; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D000431:Ethanol
keywords: Alcoholism; Cytokines; Gene expression; Lymphoblastoid cell lines; NFkappaB; TNF