Hostname: page-component-cb9f654ff-9b74x Total loading time: 0 Render date: 2025-08-04T09:27:20.193Z Has data issue: false hasContentIssue false
  • English
  • Français

Association between -174 G/C polymorphism of interleukin-6 gene and alcoholism

Published online by Cambridge University Press:  24 June 2014

Omar Šerý ,
Renáta Hladilová ,
Miroslav Novotný ,
Hana Hríbková ,
Vladimír Znojil  and
Petr Zvolský
Omar Šerý*
Affiliation:
Laboratory of Neurobiology and Molecular Psychiatry, Department of Comparative Animal Physiology and General Zoology, Masaryk University, Faculty of Science, Brno
Renáta Hladilová
Affiliation:
Laboratory of Neurobiology and Molecular Psychiatry, Department of Comparative Animal Physiology and General Zoology, Masaryk University, Faculty of Science, Brno
Miroslav Novotný
Affiliation:
Department of Psychiatry, Charles University, 1st Medical Faculty, Praha
Hana Hríbková
Affiliation:
Laboratory of Neurobiology and Molecular Psychiatry, Department of Comparative Animal Physiology and General Zoology, Masaryk University, Faculty of Science, Brno
Vladimír Znojil
Affiliation:
Department of Pathological Physiology, Masaryk University, Faculty of Medicine, Brno, Czech Republic
Petr Zvolský
Affiliation:
Department of Psychiatry, Charles University, 1st Medical Faculty, Praha
*
Laboratory of Neurobiology and Molecular Psychiatry, Department of Comparative Animal Physiology and General Zoology, Faculty of Science, Masaryk University, Kotlárská 2, 611 37 Brno, Czech Republic. Tel: + 420 541129 625; Fax: + 420 541238 815; E-mail: omarsery@sci.muni.cz
Get access Rights & Permissions [Opens in a new window]

Abstract

Objectives:

IL-6 plays the role as a physiological neuromodulator involved in dopaminergic, serotonergic and other neurotransmissions. The aim of the present association study was to examine the effect of the G/C -174 polymorphism of the IL-6 gene on disposition to alcoholism.

Methods:

We investigated the relationship between the G/C -174 polymorphism of the IL-6 gene and alcohol dependence in 281 alcoholics and 242 control subjects.

Results:

The significant difference in G allele frequency between alcoholic group (0.52) and control group (0.59) was found (P < 0.03).

Conclusion:

To our knowledge, this is the first finding providing evidence for an association between alcoholism and the polymorphism of the IL-6 gene. The background of the relationship between the IL-6 gene and alcoholism is discussed.

Keywords

alcohol dependenceassociationcytokineIL-6polymorphism

Information

Type
Research Article
Information
Acta Neuropsychiatrica , Volume 15 , Issue 5 , October 2003 , pp. 257 - 261
Copyright
Copyright © 2003 Blackwell Munksgaard

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Article purchase

Temporarily unavailable

References

Lee, YB, Nagai, A, Kim, SU. Cytokines, chemokines, and cytokine receptors in human microglia. J Neurosci Res 2002;69: 94–103.CrossRefGoogle ScholarPubMed
Sallmann, S, Juttler, E, Prinz, Set al. Induction of interleukin-6 by depolarization of neurons. J Neurosci 2000;20: 8637–8642.Google ScholarPubMed
Aloisi, F, Care, A, Borsellino, Get al.. Production of hemolymphopoietic cytokines (IL-6, IL-8, colony-stimulating factors) by normal human astrocytes in response to IL-1 beta and tumor necrosis factor-alpha. J Immunol 1992;149: 2358–2366.Google ScholarPubMed
Norris, JG, Benveniste, EN. Interleukin-6 production by astrocytes: induction by the neurotransmitter norepinephrine. J Neuroimmunol 1993;45: 137–145.CrossRefGoogle ScholarPubMed
Juttler, E, Tarabin, V, Schwaninger, M. Interleukin-6 (IL-6): a possible neuromodulator induced by neuronal activity. Neuroscientist 2002;8: 268–275.CrossRefGoogle ScholarPubMed
Zhang, J, Terreni, L, De Simoni, MG, Dunn, AJ. Peripheral interleukin-6 administration increases extracellular concentrations of serotonin and the evoked release of serotonin in the rat striatum. Neurochem Int 2001;38: 303–308.CrossRefGoogle ScholarPubMed
Wu, Y, Shaghaghi, EK, Jacquot, C, Pallardy, M, Gardier, AM. Synergism between interleukin-6 and interleukin-1beta in hypothalamic serotonin release: a reverse in vivo microdialysis study in F344 rats. Eur Cytokine Netw 1999;10: 57–64.Google ScholarPubMed
Zalcman, S, Green-Johnson, JM, Murray, Let al. Cytokine-specific central monoamine alterations following IL-1-2 and -6 administration. Brain Res 1994;643: 40–49.CrossRefGoogle Scholar
Song, C, Merali, Z, Anisman, H. Variations of nucleus accumbens dopamine and serotonin following systemic interleukin-1, interleukin-2 or interleukin-6 treatment. Neurosci 1999;88: 823–836. CrossRefGoogle ScholarPubMed
Fishman, D, Faulds, G, Jeffery, Ret al. The effect of novel polymorphisms in the interleukin-6 (IL-6) gene on IL-6 transcription and plasma IL-6 levels, and an association with systemic-onset juvenile chronic arthritis. J Clin Invest 1998;102: 1369–1376.CrossRefGoogle ScholarPubMed
Selzer, ML. The Michigan alcoholism screening test: the quest for a new diagnostic instrument. Am J Psychiatry 1971;127: 1653–1658.CrossRefGoogle ScholarPubMed
Ewing, JA. Detecting alcoholism. The CAGE Questionnaire. J Am Med Assoc 1984;252: 1905–1907. CrossRefGoogle ScholarPubMed
Gonzalez-Quintela, A, Vidal, C, Lojo, S, Perez, LF, Otero-Anton, E, Gude, F, Barrio, E. Serum cytokines and increased total serum IgE in alcoholics. Ann Allergy Asthma Immunol 1999;83: 61–67.CrossRefGoogle ScholarPubMed
Song, C, Lin, A, De Jong, Ret al. Cytokines in detoxified patients with chronic alcoholism without liver disease: increased monocytic cytokine production. Biol Psychiatry 1999;45: 1212–1216.CrossRefGoogle ScholarPubMed
Gonzalez-Quintela, A, Dominguez-Santalla, MJ, Perez, LF, Vidal, C, Lojo, S, Barrio, E. Influence of acute alcohol intake and alcohol withdrawal on circulating levels of IL-6, IL-8, IL-10 and IL-12. Cytokine 2000;12: 1437–1440.CrossRefGoogle ScholarPubMed
Maes, M, Scharpe, S, Meltzer, HY, Bosmans, E, Suy, E, Calabrese, J, Cosyns, P. Relationships between interleukin-6 activity, acute phase proteins, and function of the hypothalamic-pituitary-adrenal axis in severe depression. Psychiatry Res 1993;49: 11–27.CrossRefGoogle ScholarPubMed
Connor, TJ, Leonard, BE. Depression, stress and immunological activation: the role of cytokines in depressive disorders. Life Sci 1998;62: 583–606.CrossRefGoogle ScholarPubMed
Leu, SJ, Shiah, IS, Yatham, LN, Cheu, YM, Lam, RW. Immune-inflammatory markers in patients with seasonal affective disorder: effects of light therapy. J Affect Disord 2001;63: 27–34.CrossRefGoogle ScholarPubMed
Maes, M. Evidence for an immune response in major depression. a review and hypothesis. Prog Neuropsychopharmacol Biol Psychiatry 1995;19: 11–38.CrossRefGoogle ScholarPubMed
Maes, M, Lin, Ah, Delmeire, Let al. Elevated serum interleukin-6 (IL-6) and IL-6 receptor concentrations in posttraumatic stress disorder following accidental man-made traumatic events. Biol Psychiatry 1999;45: 833–839.CrossRefGoogle ScholarPubMed
Strauss, S, Bauer, J, Ganter, U, Jonas, U, Berger, M, Volk, B. Detection of interleukin-6 and alpha 2-macroglobulin immunoreactivity in cortex and hippocampus of Alzheimer's disease patients. Laboratory Invest 1992;66: 223–230. Google ScholarPubMed
Muller, T, Blum-Degen, D, Przuntek, H, Kuhn, W. Interleukin-6 levels in cerebrospinal fluid inversely correlate to severity of Parkinson's disease. Acta Neurol Scand 1998;98: 142–144.CrossRefGoogle ScholarPubMed
Hans, Vh, Kossmann, T, Lenzlinger, PMet al. Experimental axonal injury triggers interleukin-6 mRNA, protein synthesis and release into cerebrospinal fluid. J Cereb Blood Flow Metabol 1999;19: 184–194. CrossRefGoogle ScholarPubMed
Tarkowski, E, Rosengren, L, Blomstrand, Cet al. Early intrathecal production of interleukin-6 predicts the size of brain lesion in stroke. Stroke 1995;26: 1393–1398.CrossRefGoogle ScholarPubMed
De Simoni, MG, Perego, C, Ravizza, Tet al. Inflammatory cytokines and related genes are induced in the rat hippocampus by limbic status epilepticus. Eur J Neurosci 2000;12: 2623–2633.CrossRefGoogle ScholarPubMed
Pola, R, Flex, A, Gaetani, Eet al. The-74 G/C polymorphism of the interleukin-6 gene promoter is associated with Alzheimer's disease in an Italian population. Neuroreport 2002;13: 1645–1647.CrossRefGoogle Scholar
Shibata, N, Ohnuma, T, Takahashi, Tet al. Effect of IL-6 polymorphism on risk of Alzheimer disease: genotype–phenotype association study in Japanese cases. Am J Med Genet 2002;114: 436–439.CrossRefGoogle ScholarPubMed
Bagli, M, Papassotiropoulos, A, Knapp, Met al. Association between an interleukin-6 promoter and 3′ flanking region haplotype and reduced Alzheimer's disease risk in a German population. Neurosci Lett 2000;283: 109–112.CrossRefGoogle Scholar
Bianchi, M, Maggi, R, Pimpinelli, Fet al. Presence of a reduced opioid response in interleukin-6 knock out mice. Eur J Neurosci 1999;11: 1501–1507.CrossRefGoogle ScholarPubMed
Armario, A, Hernandez, J, Bluethmann, H, Hidalgo, J. IL-6 deficiency leads to increased emotionality in mice: evidence in transgenic mice carrying a null mutation for IL-6. J Neuroimmunol 1998;92: 160–169.CrossRefGoogle ScholarPubMed
Schafer, KH, Mestres, P, Marz, P, Rose-John, S. The IL-6/sIL-6R fusion protein hyper-IL-6 promotes neurite outgrowth and neuron survival in cultured enteric neurons. J Interferon Cytokine Res 1999;19: 527–532.CrossRefGoogle ScholarPubMed
Qiu, Z, Parsons, KL, Gruol, DL. Interleukin-6 selectively enhances the intracellular calcium response to NMDA in developing CNS neurons. J Neurosci 1995;15: 6688–6699.Google ScholarPubMed