title: Altered expression of cytokine signaling pathway genes in peripheral blood cells of alcohol dependent subjects: preliminary findings.
abstract: BACKGROUND
  Preclinical and clinical studies have implicated changes in cytokine and innate immune gene-expression in both the development of and end-organ damage resulting from alcohol dependence. However, these changes have not been systematically assessed on the basis of alcohol consumption in human subjects.
  
  
  METHODS
  Illumina Sentrix Beadchip (Human-6v2) microarrays were used to measure levels of gene-expression in peripheral blood in 3 groups of subjects: those with alcohol dependence (AD, n = 12), heavy drinkers (HD; defined as regular alcohol use over the past year of at least 8 standard drinks/wk for women and at least 15 standard drinks/wk for men, n = 13), and moderate drinkers (MD; defined as up to 7 standard drinks/wk for women and 14 standard drinks/wk for men, n = 17).
  
  
  RESULTS
  Four hundred and thirty-six genes were differentially expressed among the 3 groups of subjects (false discovery rate corrected p-value < 0.05). Two hundred and ninety-one genes differed between AD and MD subjects, 240 differed between AD and HD subjects, but only 6 differed between HD and MD subjects. Pathway analysis using DAVID and GeneGO Metacore(®) software showed that the most affected pathways were those related to T-cell receptor and Janus kinase-Signal transducer and activator of transcription (JAK-Stat) signaling.
  
  
  CONCLUSIONS
  These results suggest the transition from heavy alcohol use to dependence is accompanied by changes in the expression of genes involved in regulation of the innate immune response. Such changes may underlie some of the previously described changes in immune function associated with chronic alcohol abuse. Early detection of these changes may allow individuals at high risk for dependence to be identified.
authors.affiliation: Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut 06519, USA. robert.beech@yale.edu
authors.forename: Robert D
authors.initials: RD
authors.lastname: Beech
authors.forename: Jie
authors.initials: J
authors.lastname: Qu
authors.forename: Janine J
authors.initials: JJ
authors.lastname: Leffert
authors.forename: Aiping
authors.initials: A
authors.lastname: Lin
authors.forename: Kwangik A
authors.initials: KA
authors.lastname: Hong
authors.forename: Julie
authors.initials: J
authors.lastname: Hansen
authors.forename: Sheila
authors.initials: S
authors.lastname: Umlauf
authors.forename: Shrikant
authors.initials: S
authors.lastname: Mane
authors.forename: Hongyu
authors.initials: H
authors.lastname: Zhao
authors.forename: Rajita
authors.initials: R
authors.lastname: Sinha
mesh_terms: D000328:Adult; D000428:Alcohol Drinking / Q000235:genetics / Q000378:metabolism; D000437:Alcoholism / Q000097:blood* / Q000235:genetics; D001773:Blood Cells / Q000502:physiology*; D016207:Cytokines / Q000235:genetics / Q000502:physiology*; D003710:Demography; D039721:Diagnostic and Statistical Manual of Mental Disorders; D005006:Ethnicity; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D019409:Interleukin-15 / Q000235:genetics; D007378:Interleukins / Q000235:genetics; D053612:Janus Kinases / Q000235:genetics; D008297:Male; D046228:Microarray Analysis; D008875:Middle Aged; D012008:Recurrence; D050791:STAT Transcription Factors / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D055815:Young Adult; D000098546:Interleukin-21
chemical_list: D016207:Cytokines; D019409:Interleukin-15; D007378:Interleukins; D050791:STAT Transcription Factors; D053612:Janus Kinases; D000098546:Interleukin-21