Genética molecular del alcoholismo

Publicado

2015-07-01

Molecular genetics of alcoholism

Palabras clave:

alcoholismo, genómica, polimorfismos de nucleótido simple, farmacogenómica, epigenómica (es)
Alcoholism, Genomics, Polymorphism Single nucleotide, Pharmacogenomics, Epigenetics (en)

Descargas

PDF
HTML

Autores/as

Mauricio Rey-Buitrago Maestría en Genética Humana, Facultad de Medicina. Universidad Nacional de Colombia. Bogotá, D.C., Colombia.

Resumen (es)
Resumen (en)

El alcoholismo es una patología psiquiátrica compleja y de origen multifactorial en la que el factor genético explica alrededor del 50 % del fenómeno. Son numerosos los genes que se han asociado a esta enfermedad, pero su aporte individual es mínimo y contradictorio. Estos genes operan a través de características intermedias como la impulsividad y la sensibilidad al alcohol, lo que hace compleja la definición del fenotipo del alcoholismo. Los estudios de asociación de SNPs, de asociación a todo el genoma, de expresión y epigenéticos han identificado una amplia gama de variantes genéticas y epigenéticas, blancos para los estudios de susceptibilidad, diagnóstico y tratamiento farmacológico. Actualmente se comprenden mucho más estas relaciones y el desarrollo rápido de nuevas metodologías de estudio promete continuar este proceso, así como la generación de algoritmos de diagnóstico, prevención y tratamientos más acertados y confiables.

Alcoholism is a complex and multifactorial psychiatric pathology in which the genetic factor explains about 50% of the phenomenon. Numerous genes have been associated with the disease, but their individual contribution is minimal and contradictory. These genes operate through intermediate characteristics such as impulsivity and sensitivity to alcohol, which makes the definition of alcoholism phenotype a complex one. Association of SNPs, genome-wide association, expression and epigenetic studies have identified a wide range of genetic and epigenetic variants, targets for susceptibility studies, diagnosis and drug treatment. Currently, there is much more understanding of these relationships, and the rapid development of new methods of study promises to continue this process as well as the generation of algorithms for diagnosis, prevention and successful reliable treatments.

Descargas

Los datos de descargas todavía no están disponibles.

Citas

Organización Mundial de la Salud. Glosario de términos de alcohol y drogas. Madrid: Ministerio de Sanidad y Consumo, Centro de Publicaciones; 1994.

Babor TF, Higgins-Biddle JC, Saunders JB, Monteiro MG. AUDI: Cuestionario de Identificación de los Trastornos debidos al Consumo de Alcohol. Ginebra: Organización Mundial de la Salud, Departamento de Salud Mental y Dependencia de Sustancias; 2001.

Organización Panamericana de la Salud. Clasificación Estadística Internacional de Enfermedades y Problemas Relacionados con la Salud. 10ª revisión. Washington, D.C.: OPS, Oficina Sanitaria Panamericana; 1995.

Herran OF, Ardila MF, Barba DM. Consumo problemático de alcohol en Bucaramanga, Colombia: diseño y validación de una prueba. Biomédica. 2008 [cited 2015 Jun 29];28(1):25-37. Spanish. http://doi.org/5s9.

Organización Mundial de la Salud. Estadísticas sanitarias mundiales. Francia; 2011.

Tellez MJ, Cote MM. Alcohol etílico: un tóxico de alto riesgo para la salud humana socialmente aceptado. Rev. Fac. Med. 2006 [cited 2015 Jun 29];54(1):32-47. Spanish. Available from: http://goo.gl/7L9DCT.

Colombia. Ministerio de Justicia y Derecho, Observatorio de Drogas de Colombia, Ministerio de Salud y Protección Social, Ministerio de Educación. Estudio nacional del consumo de sustancias psicoactivas en población escolar Colombia. Bogotá; 2011.

Colombia. Ministerio de Justicia y Derecho, Observatorio de Drogas de Colombia, Ministerio de Salud y Protección Social. Estudio nacional del consumo de sustancias psicoactivas en Colombia 2013. Bogotá: ALVI Impresores S.A.S; 2014.

Programa Anti-Drogas Ilícitas de la Comunidad Andina (PRADICAN). Estudio epidemiológico Andino sobre el consumo de drogas sintéticas en la población universitaria. Lima; 2009.

Programa Anti-Drogas Ilícitas de la Comunidad Andina (PRADICAN). II Estudio epidemiológico Andino sobre consumo de drogas en la población universitaria; Informe regional. Lima; 2012.

Rehm J, Monteiro M. Alcohol consumption and burden of disease in the Americas-implications for alcohol policy. Rev Panam Salud Publica. 2005 [cited 2015 Jun 29];18(4-5):241-8. http://doi.org/ccx9n4.

Morozova TV, Mackay TF, Anholt RR. Genetics and genomics of alcohol sensitivity. Mol Genet Genomics. 2014 [cited 2015 Jun 29];289(3):253-69. http://doi.org/5tb.

Secades R, Fernández JR. Modelos de adicción. In: García E, Mendieta S, Cervera G, Fernández JR, editores. Manual SET de Alcoholismo. Madrid: Editorial Médica Panamericana; 2003. p. 19-47.

Monteiro MG, Maristela G. Alcohol y salud pública en las Américas: un caso para la acción. Washington, D.C.: OPS; 2007.

Salcedo MA. Aspectos genéticos relacionados con el alcoholismo. Típica, Boletín Electrónico de Salud Escolar. 2007 [cited 2015 Jun 29];3(2):1-8. Spanish. Available from: http://goo.gl/tuRJ2K.

Enoch MA. Genetic influences on the development of alcoholism. Curr Psychiatry Rep. 2013 [cited 2015 Jun 29];15(11):412. http://doi.org/5tc.

Sáiz PA, G-Portilla MP, Paredes MB, Bascaran MT, Bobes J. Instrumentos de evaluación en alcoholismo. Adicciones. 2002 [cited 2015 Jun 29];14 Supp 1:387-403. Spanish. Available from: http://goo.gl/E3hLMR.

World Health Organization (WHO). Global status report on alcohol and health. Library Cataloguing-in-Publication Data. Italia; 2011.

Cannon TD, Gasperoni TL, Van-Erp TG, Rosso IM. Quantitative neural indicators of liability to schizophrenia: implication for molecular genetics studies. Am J Med Genet. 2001 [cited 2015 Jun 29];105(1):16-9. http://doi.org/cdgqk4.

Chloe CY, Wong JM, Fernandes C. Drugs and addiction: an introduction to epigenetics. Addiction. 2011 [cited 2015 Jun 29];106(3):480-9. http://doi.org/b3qwcm.

Moss HB, Chiung MC, Hsiao Y. Subtypes of alcohol dependence in nationally representative sample. Drug Alcohol Depend. 2007 [cited 2015 Jun 29];91(2-3):149-58. http://doi.org/dgp98j.

Moss HB, Kirisci L, Gordon HW, Tarter RE. A neuropsychologic profile of adolescent alcoholics. Alcohol Clin Exp Res. 1994 [cited 2015 Jun 29];18(1):159-63. http://doi.org/fsxpvs.

Kreek MJ, Nielsen DA, Laforge KS. Genes associated with addiction: alcoholism, opiate, and cocaine addiction. Neuromolecular Medicine. 2004 [cited 2015 Jun 29];5(1):85-108. http://doi.org/frpmmz.

Daudén E. Farmacogenética II. Métodos moleculares de estudio, bioinformática y aspectos éticos. Actas Dermosifiliogr. 2007 [cited 2015 Jun 29];98(1):3-13. Spanish. http://doi.org/djv5sf.

Higuchi S, Matsushita S, Masaki T, Yokoyama A, Kimura M, Suzuki G, et al. Influence of genetic variations of ethanol-metabolizing enzymes on phenotypes of alcohol-related disorders. Ann N Y Acad Sci. 2004 [cited 2015 Jun 29];1025(1):472-80. http://doi.org/d36sfz.

López M, Mayorquin P, Vega M. Aplicación de los microarrays y biochips en salud humana. Madrid: Fundación Española para el Desarrollo de la Investigación en Genómica y Proteomica; 2005.

Méndez C. Tipificación de polimorfismos de los genes alcohol deshidrogenasa, aldehído deshidrogenasa y citocromo p4502E1 en una población de la ciudad de Bogotá y la evaluación de su posible asociación con el consumo problemático de alcohol [Tesis]. Bogotá: Universidad Nacional de Colombia; 2009.

Castro TX. Determinación de los polimorfismos genéticos TaqIA (ANKK1), TaqIB (DRD2), -141c ins/del (DRD2) y VNTR 40pb (DAT1) en población colombiana y evaluación de su asociación con el alcoholismo [Trabajo de Grado de Maestría]. Bogotá: Universidad Nacional de Colombia; 2013.

Hodgkinson CA, Yuan Q, Xu K, Shen PH, Heinz E, Lobos EA, et al.Addictions biology: haplotype-based analysis for 130 candidate genes on a single array. Alcohol Alcohol. 2008 [cited 2015 Jun 29];43(5):505-15. http://doi.org/bqn4dn.

Heinz A. Dopaminergic dysfunction in alcoholism and schizophrenia-psycopathological and behavioral correlates. Eur Psychiatry. 2002 [cited 2015 Jun 29];17(1):9-16. http://doi.org/b5nkwx.

Volkov ND, Fowler JS, Wang GJ. The addicted human brain viewed in the light of imaging studies: brain circuits and treatment strategies. Neuropharmacology. 2004 [cited 2015 Jun 29];47 Suppl 1:3-13. http://doi.org/dttmvm.

Flatscher BT, Harrison E, Matsumoto I, Wilce PA. Genes associated with alcohol abuse and tobacco smoking in the human nucleus accumbens and ventral tegmental area. Alcohol Clin Exp Res. 2010 [cited 2015 Jun 29];34(7):1291-302. http://doi.org/b2fxn5.

Kimura M, Higuchi S. Genetics of alcohol dependence. Psychiatry and Clinical Neurosciences. 2011 [cited 2015 Jun 29];65(3):213-25. http://doi.org/ffzbcn.

Köhnke MD, Batra A, Kolb W, Köhnke AM, Lutz U, Schick S, et al. Association of the dopamine transporter gene with alcoholism. Alcohol Alcohol. 2005 [cited 2015 Jun 29];40(5):339-42. http://doi.org/fmdq6v.

Enoch MA, Xu K, Ferro E, Harris CR, Goldman D. Genetic origins of anxiety in women: a role for a functional catechol-O-methyltransferase polymorphism. Psychiatr Genet. 2003 [cited 2015 Jun 29];13(1):33-41. http://doi.org/ctvgdg.

Choi IG, Kee BS, Son HG, Ham BJ, Yang BH, Kim SH, et al. Genetic polymorphisms of alcohol and aldehyde dehydrogenase, dopamine and serotonin transporters in familial and non-familial alcoholism. Eur Neuropsychopharmacol. 2006 [cited 2015 Jun 29];16(2):123-8. http://doi.org/dsrfg7.

Izquierdo M. Intoxicación alcohólica aguda. Adicciones. 2002 [cited 2015 Jun 29];14 Supp 1:175-93. Available from: http://goo.gl/08Ai1q.

Xuei X, Dick D, Flury-Wetherill L, Tian HJ, Agrawal RG, Bierut LJ, et al. Association of the kappa-opioid system with alcohol dependence. Mol Psychiatry. 2006 [cited 2015 Jun 29];11(11):1016-24. http://doi.org/b26kdx.

Méndez M, Morales M. Role of mu and delta opioid receptors in alcohol drinking behaviour. Curr Drug Abuse Rev. 2008 [cited 2015 Jun 29];1(2):239-52. http://doi.org/fpgs3h.

Kalivas PW, Volkow ND. The neural basis of addition: A pathological of motivation and choice. Am J Psychiatry. 2005 [cited 2015 Jun 29];162(8):1403-13. http://doi.org/cb3rdc.

Singh SM, Treadwell J, Kleiber ML, Harrison M, Uddin RK. Analysis of behavior using genetical genomics in mice as a model: from alcohol preferences to gene expression differences. Genome. 2007 [cited 2015 Jun 29];50(10):877-97. http://doi.org/ccvdgf.

Tabakoff B, Saba L, Printz M, Flodman P, Hodgkinson C, Goldman D, et al. Genetical genomic determinants of alcohol consumption in rats and Humans. BMC Biol. 2009 [cited 2015 Jun 29];7(1):70. http://doi.org/djc8z6.

Robison AJ, Nestler EJ. Transcriptional and epigenetic mechanism of addition. Nat Rev Neurosci. 2011 [cited 2015 Jun 29];12(11):623-37. http://doi.org/fbncv5.

Fei SS. Integrating genetics and protemics to study alcohol-drinking behavior [dissertation]. School of Medicine, Oregon Health & Science University: Student Scholar Archive; 2011. Paper 588.

Gelernter J, Kranzler HR, Sherva R, Almasy L, Koesterer R, Smith AH, et al. Genome-wide association study of alcohol dependence: significant findings in African- and European-Americans including novel risk loci. Mol Psychiatry. 2014 [cited 2015 Jun 29];19(1):41-9. http://doi.org/5td.

Kelley KW, Dantzer R. Alcoholism and inflammation: Neuroimmunology of behavioral and mood disorders. Brain Behav Immun. 2011 [cited 2015 Jun 29];25 Supp 1:S13-20. http://doi.org/csrv54.

Lehrmann E, Colantuoni C, Deep-Soboslay A, Becker KG, Lowe R, Huestis M, et al. Transcriptional changes common to human cocaine, cannabis and phencyclidine abuse. PLoS One. 2006 [cited 2015 Jun 29];1(1):e114. http://doi.org/fpb55r.

Levey DF, Le-Niculescu J, Ayalew M, Jain N, Kirlin K, Learman R, et al. Genetic risk prediction and neurobiological understanding of alcoholism. Transl Psychiatry. 2014 [cited 2015 Jun 29];4(5):e391. http://doi.org/5tf.

Mayfield RD, Lewohl JM, Dodd PR, Herlihy A, Liu J, Harris RA. Patterns of gene expression are altered in the frontal and motor cortices of human alcoholics. J Neurochem. 2002 [cited 2015 Jun 29];81(4):802-13. http://doi.org/fjn7dx.

Sohma H, Hashimoto E, Shirasaka T, Tsunematsu R, Ozawa H, Boissl K, et al. Quantitative reduction of type I adenylyl cyclase in human alcoholics. Biochim Biophys Acta. 1999 [cited 2015 Jun 29];1454(1):11-8. http://doi.org/fskqj7.

Zhang R, Miao Q, Wang C, Zhao R, Li W, Haile CN, et al. Genomic-wide DNA metilation analysis in alcohol dependence. Addict Biol. 2013 [cited 2015 Jun 29];18(2):392-403. http://doi.org/5tg.

Franklin TB, Mansuy IM. Epigenetic inheritance in mammals: evidence for the impact of adverse environmental effects. Neurobiol Dis. 2010 [cited 2015 Jun 29];39(1):61-5. http://doi.org/d6pt46.

Zhang H, Herman AI, Kranzler HR, Anton RF, Zhao H, Zheng W, et al. Array-based profiling of DNA methylation changes associated with alcohol dependence. Alcohol Clin Exp Res. 2013 [cited 2015 Jun 29];37 Supp 1: E108-15. http://doi.org/5th.

Girardot M, Feil R, Llères D. Epigenetic deregulation of genomic imprinting in humans: causal mechanisms and clinical implications. Epigenomics. 2013 [cited 2015 Jun 29];5(6):715-28. http://doi.org/5tj.

Razvi E. Epigenetic research classes and assay trends. GEN Reports: Market & Tech Analysis. 2013 [cited 2015 Jun 29];33(3):1-10. Available from: http://goo.gl/dcl9vW.

Tatarinova T, Owain K. DNA Methylation-from genomics to technology. Rijeka, Croatia: InTech; 2012.

Zhou L, Cheng X, Connolly BA, Dickman MJ, Hurd PJ, Hornby DP. Zebularine: a novel DNA methylation inhibitor that forms a covalent complex with DNA methyltransferases. J Mol Biol. 2002 [cited 2015 Jun 29];321(4):591-9. http://doi.org/cs27bj.

Shakharka AJ, Zhang H, Tang L, Shi G, Pandey SC. Histone deacetylases (HDAC)-induced histone modifications in the amygdala: a role in rapid tolerance to the anxiolytic effects of ethanol. Alcohol Clin Exp Res. 2012 [cited 2015 Jun 29];36(1):61-71. http://doi.org/dh9rc3.

Zakhari S. Alcohol metabolism and epigenetics changes. Alcohol Res. 2013 [cited 2015 Jun 29];35(1):6-16. Available from: http://goo.gl/F9kPSh.

Wasielewski JA, Holloway FA. Alcohol's Interactions with Circadian Rhythms. A focus on body temperature. Alcohol Res Health. 2001 [cited 2015 Jun 29]; 25(2):94-100. Available from: http://goo.gl/30sh2a.

Andrés G, Ashour N, Sánchez-Chapado M, Ropero S, Angulo JC. The study of DNA methylation in urological cancer: present and future. Actas Urol Esp. 2013 [cited 2015 Jun 29];37(6):368-75. http://doi.org/f2jkfj.

Shukla SD, Zakhari S. Epigenetics: new frontier for alcohol research. Alcohol Res. 2013 [cited 2015 Jun 29];35(1):1-2. Available from: http://goo.gl/wqTBaB.

Fuller RK, Branchey L, Brightwell DR, Derman RM, Emrick CD, Iber FL, et al. Disulfiram treatment of alcoholism: a Veterans Administration cooperative study. JAMA. 1986 [cited 2015 Jun 29];256(11):1449-55. http://doi.org/bzhvsf.

Caputo F, Vignoli T, Grignaschi A, Cibin M, Addolorato G, Bernandi M. Pharmacological management of alcohol dependence: From mono-therapy to pharmacogenetics and beyond. Eur Neuropsychopharmacol. 2014 [cited 2015 Jun 29];24(2):181-91. http://doi.org/5tk.

Whitworth AB, Oberbauer H, Fleischhacker WW, Lesch OM, Walter H, Nimmerrichter A, et al. Comparison of acamprosate and placebo in long-term treatment of alcohol dependence. Lancet. 1996 [cited 2015 Jun 29];347(9013): 1438-42. http://doi.org/fp46fd.

Kranzler HR, Van-Kirk J. Efficacy of naltrexone and acamprosate for alcoholism treatment: A meta-analysis. Alcohol Clin Exp Res. 2001 [cited 2015 Jun 29];25(9):1335-41. http://doi.org/c59s2h.

Selinn J. Implementation of substitution treatment in Finland: Beyond rationalisation and medicalisation. Nordic Studies on Alcohol and Drugs. 2011 [cited 2015 Jun 29];28(1): 29-42. http://doi.org/fgqr4c.

Camilleri M. Pharmacogenomics and serotonergic agents: research observations and potential clinical practice implications. Neurogastroenterol Motil. 2007 [cited 2015 Jun 29];19 Supp 2:40-5. http://doi.org/dv8c36.

Pettinati HM, Volpicelli JR, Kranzler HR, Luck G, Rukstalis MR, Cnaan A. Sertraline treatment for alcohol dependence: interactive effects of medication and alcoholic subtype. Alcohol Clin Exp Res. 2000 [cited 2015 Jun 29];24(7):1041-9. http://doi.org/cwdwsc.

Caputo F, Francini S, Brambilla R, Vigna-Taglianti F, Stoppo M, Del Re A, et al. Sodium oxybate in maintaining alcohol abstinence in alcoholic patients with and without psychiatric comorbidity. Eur Neuropsychopharmacol. 2011 [cited 2015 Jun 29];21(6): 450-6. http://doi.org/fgxhsd.

Johnson BA, Ait-Daoud N, Bowden CL, DiClemente CC, Roache JD, Lawson K, et al. Oral topiramate for treatment of alcohol dependence: a randomised controlled trial. Lancet. 2003 [cited 2015 Jun 29];361(9370):1677-85. http://doi.org/dv6cvm.

Martinotti G, Di Nicola M, Di Giannantonio M, Janiri L. Aripiprazole in the treatment of patients with alcohol dependence: a double-blind, comparison trial vs. naltrexone. J Psychopharmacol. 2009 [cited 2015 Jun 29];23(2):123-9. http://doi.org/dzk3pq.

Colombo G, Orrù A, Lai P, Cabras C, Maccioni P, Rubio M, et al. The cannabinoid CB1 receptor antagonist, rimonabant, as a promising pharmacotherapy for alcohol dependence: preclinical evidence. Mol Neurobiol. 2007 [cited 2015 Jun 29];36(1):102-12. http://doi.org/b7dfbk.

Lawford BR, Young RM, Rowell JA, Qualichefski J, Fletcher BH, Syndulko K. Bromocriptine in the treatment of alcoholics with the D2 dopamine receptor A1 allele. Nat Med. 1995 [cited 2015 Jun 29];1(4):337-41. http://doi.org/fb5mz3.

Furieri FA, Nakamura-Palacios EM. Gabapentin reduces alcohol consumption and craving: a randomized, double-blind, placebo-controlled trial. J Clin Psychiatry. 2007 [cited 2015 Jun 29];68(11):1691-700. http://doi.org/d8kcv9.

Kranzler HR, McKay JR. Personalized treatment of alcohol dependence. Curr Psychiatry Rep. 2012 [cited 2015 Jun 29];14(5):486-93. http://doi.org/5tm.

Becerril VE, Moreno AJ, Mendieta CD, González CD, Natera RG, Pavón RL, et al. Estudio preliminar de la expresión del mensaje genético del transportador de serotonina en células mononucleares de sangre periférica en pacientes con dependencia al alcohol con y sin depresión mayor comórbida. Salud Mental. 2011 [cited 2015 Jun 29];34(2):139-47. Spanish. Available from: http://goo.gl/WZT5dk.

Agrawal RG, Owen JA, Levin PS, Hewetson A, Berman AE, Franklin SR, et al. Bioinformatics analyses reveal age-specific neuroimmune modulation as a target for treatment of high ethanol drinking. Alcohol Clin Exp Res. 2014 [cited 2015 Jun 29];38(2):428-37. http://doi.org/5tn.

Ray L, Bryan A, MacKillop J, McGeary J, Hesterberg K, Hutchison KE. The dopamine D4 receptor (DRD4) gene exon III polymorphism, problematic alcohol use and novelty seeking: direct and mediated genetic effects. Addict Biol. 2009 [cited 2015 Jun 29];14(2):238-44. http://doi.org/fn7wzt.

Licencia

Derechos de autor 2015 Revista de la Facultad de Medicina

Esta obra está bajo una licencia Creative Commons Reconocimiento 3.0 Unported.