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Genetic association between −93A/G polymorphism in the Fyn kinase gene and alcohol dependence in Spanish men

Published online by Cambridge University Press:  16 April 2020

Isabel J. Pastor
Affiliation:
Unidad de Medicina Molecular, Departamento de Medicina, Universidad de Salamanca, Avda. de Alfonso X el Sabio s/n, 37007Salamanca, Spain Unidad de Alcoholismo, Servicio de Medicina Interna, Hospital Universitario de Salamanca, Universidad de Salamanca, Salamanca, Spain
F. Javier Laso
Affiliation:
Unidad de Alcoholismo, Servicio de Medicina Interna, Hospital Universitario de Salamanca, Universidad de Salamanca, Salamanca, Spain
Sandra Inés
Affiliation:
Unidad de Medicina Molecular, Departamento de Medicina, Universidad de Salamanca, Avda. de Alfonso X el Sabio s/n, 37007Salamanca, Spain Unidad de Alcoholismo, Servicio de Medicina Interna, Hospital Universitario de Salamanca, Universidad de Salamanca, Salamanca, Spain
Miguel Marcos
Affiliation:
Unidad de Medicina Molecular, Departamento de Medicina, Universidad de Salamanca, Avda. de Alfonso X el Sabio s/n, 37007Salamanca, Spain Unidad de Alcoholismo, Servicio de Medicina Interna, Hospital Universitario de Salamanca, Universidad de Salamanca, Salamanca, Spain
Rogelio González-Sarmiento*
Affiliation:
Unidad de Medicina Molecular, Departamento de Medicina, Universidad de Salamanca, Avda. de Alfonso X el Sabio s/n, 37007Salamanca, Spain
*
*Corresponding author. Tel.: +34 923294553; fax: +34 923394593. E-mail address: [email protected] (R. González-Sarmiento).
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Abstract

Background

Fyn tyrosine kinase is a member of the Scr family that phosphorylates the NR2A and NR2B subunits of the NMDA receptors reducing the inhibitory effects of ethanol and therefore may regulate the individual sensitivity to ethanol.

Objectives

To investigate whether there is any relationship between the polymorphism at position −93 of the Fyn kinase gene and the susceptibility to develop alcoholism.

Methods

We studied the distribution of genotypes and alleles of the polymorphism −93A/G (137346 T/C) in the 5′ UTR region of the fyn gene in 207 male heavy drinkers (119 with alcohol dependence and 88 with alcohol abuse) and 100 control subjects from Castilla y León (Spain).

Results

The frequency of G allele carriers was higher in alcohol dependents than in alcohol abusers (47.9% vs 30.6%; p = 0.015; OR = 2.077; 95% CI 1.165–3.704).

Conclusion

Our results show that the −93G allele of Fyn kinase gene is associated with higher risk to develop alcohol dependence in Spanish men.

Type
Original article
Copyright
Copyright © Elsevier Masson SAS 2009

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References

Allgaier, C.Ethanol sensitivity of NMDA receptors. Neurochem Int 2002;41:377382CrossRefGoogle ScholarPubMed
American Psychiatric Association, Diagnostic and statistical manual of mental disorders (DSM-IV) 4th ed.Washington, DCAPA 1994Google Scholar
Bierut, L.J., Dinwiddie, S.H., Begleiter, H., Crowe, R.R., Hesselbrock, V., Nurnberger, J.I. Jr.et al.Familial transmission of substance dependence: alcohol, marijuana, cocaine, and habitual smoking: a report from the Collaborative Study on Genetics of Alcoholism. Arch Gen Psychiatry 1998;55:982988CrossRefGoogle Scholar
Boehm, S.L.2ndPeden, L., Chang, R., Harris, R.A., Blednov, Y.A.Deletion of the fyn-kinase gene alters behavioral sensitivity to ethanol. Alcohol Clin Exp Res 2003;27:10331040CrossRefGoogle Scholar
Boyle, J.M., Hey, Y., Myers, K., Stern, P.L., Grzeschik, F.H., Ikehara, Y.et al.Regional localization of a trophoblast antigen-related sequence and 16 other sequences to human chromosomes 6q using somatic cell hybrids. Genomics 1992;12:693698CrossRefGoogle ScholarPubMed
Cantor, R.M., Lanning, C.D.Comparison of evidence supporting a chromosome 6 alcoholism gene. Genet Epidemiol 1999;17(Suppl.):S91S96CrossRefGoogle ScholarPubMed
Cheung, H.H., Gurd, J.W.Tyrosine phosphorylation of the N-methyl-d-aspartate receptor by exogenous and postsynaptic density-associated Scr-family kinases. J Neurochem 2001;78:524534CrossRefGoogle Scholar
Colhoun, H.M., McKeigue, P.M., Davey Smith, G.Problems of reporting genetic associations with complex outcomes. Lancet 2003;361:865872CrossRefGoogle ScholarPubMed
Daly, A.K., Day, C.P.Candidate gene case-control association studies: advantages and potential pitfalls. Br J Clin Pharmacol 2001;52:489499CrossRefGoogle ScholarPubMed
Dick, D.M., Foroud, T.Candidate genes for alcohol dependence: a review of genetic evidence from human studies. Alcohol Clin Exp Res 2003;27:868879CrossRefGoogle ScholarPubMed
Fadda, F., Rossetti, Z.L.Chronic ethanol consumption: from neuroadaptation to neurodegeneration. Prog Neurobiol 1998;56:385431CrossRefGoogle ScholarPubMed
Fink, K., Gothert, M.Both ethanol and ifenprodil inhibit NMDA-evoked release of various neurotransmitters at different, yet proportional potency: potential relation to NMDA receptor subunit composition. Naunyn Schmiedebergs Arch Pharmacol 1996;354:312319CrossRefGoogle ScholarPubMed
Harada, S., Agarwal, D.P., Nomura, F., Higuchi, S.Metabolic and ethnic determinants of alcohol drinking habits and vulnerability to alcohol-related disorder. Alcohol Clin Exp Res 2001;25(Suppl. 5):71S75SCrossRefGoogle ScholarPubMed
Ishiguro, H., Saito, T., Shibuya, H., Toru, M., Arinami, T.Mutation and association analysis of the Fyn kinase gene with alcoholism and schizophrenia. Am J Med Genet Neuropsychiatr Genet 2000;96:716720Google Scholar
Kumari, M., Ticku, M.K.Regulation of NMDA receptors by ethanol. Prog Drug Res 2000;54:152189Google ScholarPubMed
Masood, K., Wu, C., Brauneis, U., Weight, F.F.Differential ethanol sensitivity of recombinant N-methyl-d-aspartate receptor subunits. Mol Pharmacol 1994;45:324329Google ScholarPubMed
Miyakawa, T., Yagi, T., Kitazawa, H., Yasuda, M., Kawai, N., Tsuboi, K.et al.Fyn-kinase as a determinant of ethanol sensitivity: relation to NMDA-receptor function. Science 1997;278:698701CrossRefGoogle ScholarPubMed
Pastor, I.J., Laso, F.J., Avila, J.J., Rodríguez, R.E., González-Sarmiento, R.Polymorphism in the interleukin-1 receptor antagonist gene is associated with alcoholism in Spanish men. Alcohol Clin Exp Res 2000;24:14791482CrossRefGoogle ScholarPubMed
Pastor, I.J., Laso, F.J., Romero, A., González-Sarmiento, R.Interleukin-1 gene cluster polymorphisms and alcoholism in Spanish men. Alcohol Alcohol 2005;40:181186CrossRefGoogle ScholarPubMed
Pastor, I.J., Laso, F.J., Romero, A., González-Sarmiento, R.−238 G>A polymorphism of tumor necrosis factor alpha gene (TNFA) is associated with alcoholic liver cirrhosis in alcoholic Spanish men. Alcohol Clin Exp Res 2005;29:19281931CrossRefGoogle ScholarPubMed
Reich, T., Hinrichs, A., Culverhouse, R., Bierut, L.Genetic studies of alcoholism and substance dependence. Am J Hum Genet 1999;65:599605CrossRefGoogle ScholarPubMed
Resh, M.D.Fyn, a Src family tyrosine kinase. Int J Biochem Cell Biol 1998;30:11591162CrossRefGoogle ScholarPubMed
Schumann, G., Rujescu, D., Kissling, C., Soyka, M., Dahmen, N., Preuss, U.W.et al.Analysis of genetic variations of protein tyrosine kinase fyn and their association with alcohol dependence in two independent cohorts. Biol Psychiatry 2003;54:14221426CrossRefGoogle ScholarPubMed
Spanagel, R., Bienkowski, P.Alcohol dependence and addictionLodge, D., Danysz, W., Parsons, C.G.Ionotropic glutamate receptors as therapeutic targets Johnson City, TNF.P. Graham Publishing Co. 2002 375403Google Scholar
Tezuka, T., Umemori, H., Akiyama, T., Nakanishi, S., Yamamoto, T.PSD-95 promotes Fyn-mediated tyrosine phosphorylation of the N-methyl-d-aspartate receptor subunit NR2A. Proc Natl Acad Sci U S A 1999;96:435440CrossRefGoogle ScholarPubMed
Tsai, G., Coyle, J.Y.The role of glutamatergic neurotransmission in the pathophysiology of alcoholism. Annu Rev Med 1998;49:173184CrossRefGoogle ScholarPubMed
Yaka, R., Phamluong, K., Ron, D.Scaffolding of Fyn kinase to the NMDA receptor determines brain region sensitivity to ethanol. J Neurosci 2003;23:36233632CrossRefGoogle Scholar
Zhao, W., Cavallaro, S., Gusev, P., Alkon, D.L.Non-receptor tyrosine protein kinase pp60c-src in spatial learning: synapse-specific changes in its gene expression, tyrosine phosphorylation and protein–protein interactions. Proc Natl Acad Sci U S A 2000;97:80988103CrossRefGoogle Scholar
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