Altered Expression of Cytokine Signaling Pathway Genes in Peripheral Blood Cells of Alcohol Dependent Subjects: Preliminary Findings

• Published in: Alcoholism, clinical and experimental research Vol. 36; no. 9; pp. 1487 - 1496
• Main Authors: Beech, Robert D., Qu, Jie, Leffert, Janine J., Lin, Aiping, Hong, Kwangik A., Hansen, Julie, Umlauf, Sheila, Mane, Shrikant, Zhao, Hongyu, Sinha, Rajita
• Format: Journal Article
• Language: English
• Published: Hoboken, NJ Blackwell Publishing Ltd 01.09.2012; Wiley; Wiley Subscription Services, Inc
• Subjects: Addictive behaviors; Adult; Adult and adolescent clinical studies; Alcohol Dependence; Alcohol Drinking - genetics; Alcohol Drinking - metabolism; Alcohol use; Alcoholism; Alcoholism - blood; Alcoholism - genetics; Alcoholism and acute alcohol poisoning; Biological and medical sciences; Blood Cells - physiology; Cytokines - genetics; Cytokines - physiology; Demography; Diagnostic and Statistical Manual of Mental Disorders; Ethnic Groups; Female; Gene Expression; Gene Expression Profiling; Genes; Humans; IL-15; IL-21; Immune system; Interleukin-15 - genetics; Interleukins - genetics; Janus Kinase; Janus Kinases - genetics; Male; Medical sciences; Microarray; Microarray Analysis; Middle Aged; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Recurrence; Signal Transducer and Activator of Transcription; Signal Transduction - genetics; Signal Transduction - physiology; STAT Transcription Factors - genetics; Toxicology; Young Adult; Human; Jak protein tyrosine kinase; Transcription; Toxicity; Alcoholism; Cytokine; DNA chip; IL-15; Interleukin 15; Microarray; IL-21; Alcoholic beverage; Signal transduction; Signal Transducer and Activator of Transcription; Blood cell; Janus Kinase; Addiction; Gene; Signaling pathway; Activator; Dependence; Interleukin 21; Genetics; Alcohol Dependence
• ISSN: 0145-6008; 1530-0277
• DOI: 10.1111/j.1530-0277.2012.01775.x

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.