Hostname: page-component-cd9895bd7-jn8rn Total loading time: 0 Render date: 2024-12-23T08:46:56.213Z Has data issue: false hasContentIssue false

Nueva apreciación de la asociación entre el gen del DRD2, el alcoholismo y la adicción

Published online by Cambridge University Press:  12 May 2020

P. Gorwood
Affiliation:
Laboratorio de Epidemiología Genética (Unidad 155 del INSERM), París
P. Batel
Affiliation:
Unidad de Tratamiento Ambulatorio de las Enfermedades Alcohólicas”; “Centro de Transfusión de Sangre”, Hospital Beaujon, París
L Gouya
Affiliation:
Laboratorio de Bioquímica (Federación de Biología Molecular, Unidad 409 del INSERM), Hospital Louis Mourier, 178 ruédes Renouillers,92701Colombes
F. Courtois
Affiliation:
“Centro de Transfusió n de Sangre”, Hospital Beaujon (Asistencia Pública-Hospitales de París),París, Francia.
J. Feingold
Affiliation:
Laboratorio de Epidemiología Genética (Unidad 155 del INSERM), París
J. Adés
Affiliation:
Departamento Psiquiátrico, Laboratory de Bioquímica, Hospital Louis Mourier, 178 ruédes Renouillers, 92701Colombes
Get access

Resumen

Analizamos el efecto del alelo Al Taql del gen del receptor D2 de dopamina sobre el ries-go de alcoholismo, intentando representar tres explicaciones propuestas con frecuencia para explicar las discrepancias en los estudios de asociación y ligamiento: que el alelo Al puede actuar como un marca-dor más bien que como un factor de vulnerabilidad, que los sesgos de estratificación y los controles no evaluados pueden explicar los resultados positivos, y que el alelo Al modifica el genotipo en lugar de aumentar el riesgo de alcoholismo. Así, examinamos otro marcador (STRP de dinucleótidos) dentro del gen del DRD2, seleccionamos una nueva muestra homogénea de 113 pacientes alcohólicos y 49 controles no afectados emparejados estrictamente en cuanto a los orígenes étnicos y evaluamos sistemáti-camente ambas muestras con una entrevista semiestructurada para detectar (en ambas) la dependencia de alcohol, pero también rasgos relacionados tales como complicaciones específicas. La frecuencia del alelo Al no era significativamente diferente entre los alcohólicos y los controles, pero cuando se com-pararon subgrupos diferentes de alcohólicos, el alelo Al fue significativamente más frecuente en los pacientes alcohólicos con complicaciones somáticas (RV = 3,00, IC [1,37 - 6,62]), con complicaciones sociales y profesionales (RV = 2,72, IC [1,25 - 5,90]) o con dependencia comórbida (RV = 2,88, IC 95% [1,16 - 7,15]). La asociación para la dependencia comórbida y las complicaciones somáticas fue positiva también cuando se tomaron en consideración tanto los STRP como los polimorfismos TaqIA. El alelo Al no aumenta el riesgo de alcoholismo per se en nuestra muestra, pero puede estar implicado en un rasgo relacionado que es parcialmente dependiente del diagnóstic de alcoholismo, a través de un desequilibrio con otra mutación próxima.

Type
Artículo original
Copyright
Copyright © European Psychiatric Association 2000

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.)

References

Bibliografía

Amadeo, SAbbar, MFourcade, MLWacksman, GLeroux, MMadec, A, et al. D2 dopamine receptor gene and alcoholism. J Psychiat Res 1993; 2: 173–9.CrossRefGoogle Scholar
Barr, CLKidd, KK.Population frequencies of the Al alíele at the dopamine D2 receptor locus. Biol Psychiatry 1993; 31: 285.Google Scholar
Blum, KNoble, ESheridan, PMontgomery, ARitchie, TOzkaragoz, T, et al. Genetic predisposition in alcoholism: association of the D2 dopamine receptor Taql B1 RFLP with severe alcoholics. Alcohol 1993; 10: 5967.CrossRefGoogle Scholar
Blum, KSheridan, PWood, RBracermann, EChen, TComings, D.Dopamine D2 receptor gene variants: association and linkage studies in impulsive-addictive-compulsive behaviour. Pharmacogenetics 1995; 5: 121–41.CrossRefGoogle ScholarPubMed
Bohman, M.Some genetic aspects of alcoholism and criminality: A population of adoptees. Arch Gen Psychiatry 1978; 35: 269–76.CrossRefGoogle ScholarPubMed
Bolos, ADean, MLucs-Derse, SRamsburg, MBrown, GGoldman, D.Population and pedigree studies reveal a lack of association between the dopamine D2 receptor gene and alcoholism. JAMA 1990; 264: 3156–60.CrossRefGoogle ScholarPubMed
Cloninger, C.D2 dopamine receptor gene is associated but not linked with alcoholism. JAMA 1991; 266: 1833–4.CrossRefGoogle Scholar
Comings, DComings, BDonn Muhleman, MS, et al. The dopamine D2 receptor locus as a modifying gene in neu-ropsychiatric disorders. JAMA 1991; 266: 17931800.CrossRefGoogle ScholarPubMed
Cook, CGurling, H.The D2 dopamine receptor gene and alcoholism: a genetic effect on the liability of alcoholism. J R Soc Med 1994; 87: 400–2.Google ScholarPubMed
Cook, CPalsson, GTurner, AHomes, DBrett, PCurtis, D, et al. A genetic linkage study of the D2 dopamine receptor locus in heavy drinking and alcoholism. Br J Psychiatry 1996; 169: 243–8.CrossRefGoogle ScholarPubMed
Cotton, NS.The familial incidence of alcoholism. A review. J Stud Alcohol 1979; 40: 89116.CrossRefGoogle ScholarPubMed
Coughlin, SBenichou, JWeed, D.Attributable risk estimation in case-control studies. Epidemiol Rev 1994; 16: 5164.CrossRefGoogle ScholarPubMed
Cruz, CCamarena, BMejia, JPaez, FEroza, VRamón, DELa Fuente, R, et al. The dopamine D2 receptor gene Taql Al polymorphism and alcoholism in a Mexican population. Arch Med Res 1995; 26: 421–6.Google Scholar
Debrettes, BBerlín, ILaurent, CLépine, JPMallet, JPuech, A.The dopamine D2 receptor gene Taql A polymorphism is not associated with novelty seeking, harm avoidance and reward dependence in healthy subjects. Eur Psychiatry 1998; 13: 427–30.CrossRefGoogle Scholar
Finckh, UGiraldo Velasquez, MPelz, JOtto, GSander, TSchmidt, L, et al. Dopamine D2 receptor gene (DRD2): haplotypes in caucasians. Gene 1996; 179: 251–5.CrossRefGoogle ScholarPubMed
Gelertner, JO’Malley, SRisch, NKranzler, HKrystal, JMerikangas, K, et al. No association between an alíele at the D2 dopamine receptor gene (D2) and alcoholism. JAMA 1991; 266: 1801–7.Google Scholar
Goldman, DBrown, GLAlbaugh, BRobín, RGoodson, STrunzo, M, et al. D2 dopamine receptor genotype, linkage disequilibrium, an alcoholism in American Indians and other populations. Alcohol Clin Exp Res 1993; 17: 199204.CrossRefGoogle ScholarPubMed
Goldman, DUrbanek, MGuenther, DRobin, RLong, JC.Linkage and association of a functional DRD2 variant [Ser311Cys] and DRD2 markers to alcoholism, substance abuse and schiziphrenia in southwestern American Indians. Am J Med Gen 1997; 74: 386–94.3.0.CO;2-N>CrossRefGoogle Scholar
Gorwood, PAdés, JFeingold, J.Are genes coding for dopamine receptors implicated in alcoholism? Eur Psychiatry 1994; 9: 63–9.CrossRefGoogle Scholar
Gorwood, P.Genetic association studies in behavioral neuroscience. In: Cruzio, WGerlai, R, eds. Molecular genetic techniques for behavioural neuroscience. Amsterdam: Elsevier; 1999.Google Scholar
Grandy, DKZhang, YCivelli, O.PCR detection of the TaqA RFLP at the DRD2 locus. Hum Mol Genet 1993; 2: 2197.CrossRefGoogle ScholarPubMed
Hauge, XYGrandy, DKEubanks, JHEvans, GACivelli, OLitt, M.Detection and characterisation of additional DNA polymorphisms in the dopamine D2 receptor gene. Genomics 1991; 10: 527–30.CrossRefGoogle Scholar
Koob, GF, Drugs of abuse: anatomy, pharmacology and function of reward pathways. Trends Pharmacol Sci 1992; 13: 177–84.CrossRefGoogle ScholarPubMed
Lawford, BYoung, RRowell, JGibson, JFeeney, GRitchie, T, et al. Association of the D2 dopamine receptor Al alíele with alcoholism: medical severity of alcoholism and type of Controls. Biol Psychiatry 1997; 41: 385–93.CrossRefGoogle Scholar
Loparev, VNCartas, MAMonken, CVelpandi, ASrinivajan, A.An efflcient and simple method of DNA extraction from whole blood and cell lines to identify infectious agents. J Virol Methods 1991; 34: 105–12.CrossRefGoogle Scholar
Neiswanger, KHoll, SYKapan, BB.Association and linkage studies of the TAQ1A1 alíele at the dopamine D2 receptor gene in samples of female and male alcoholics. Am J Med Gen 1995; 60: 267–71.CrossRefGoogle Scholar
Neiswanger, KKaplan, BBHill, SY.What can the D2/alco-holism story teach us about association studies in psychiatric genetics? Am J Med Gen 1995; 60: 272–5.CrossRefGoogle ScholarPubMed
Noble, ESyndulko, KFitch, JRitchie, TBohlman, MGuth, P, et al. D2 dopamine receptor Taql A alíeles in medically ill alcoholic and nonalcoholic patients. Alcohol Alcohol 1994; 29: 729–44.Google Scholar
Noble, EP.The D2 dopamine receptor gene: review of association studies in alcoholism. Behav Genet 1993; 23: 119–29.CrossRefGoogle ScholarPubMed
Noble, EP.Alcoholism and the dopaminergic system: a review. Addict.Biology 1996; 1: 333–48.CrossRefGoogle ScholarPubMed
Noble, EPBlum, KKhalsa, MRitchie, TMontgomery, AWood, R, et al. Allelic association of the D2 dopamine receptor gene with cocaine dependence. Drug Alcohol Depend 1993; 33: 271–85.CrossRefGoogle ScholarPubMed
Nurnberger, JIBlehar, MCKaufmann, CAYork-Cooler, CSimpson, SGHarkavy-Friedman, J, et al. Diagnostic Interview for Genetic Studies: rational, unique features, and training. Arch Gen Psychiatry 1994; 51: 849–62.CrossRefGoogle Scholar
Parsian, ATodd, RDevor, EO’Malley, KSuarez, BReich, T, et al. Alcoholism and alíeles of the human D2 dopamine receptor locus. Arch Gen Psychaitry 1991; 48: 655–63.CrossRefGoogle Scholar
Pato, CMacciardi, FPato, MVerga, MKennedy, H.Review of the putative association of the DRD2 and alcoholism: a metaanalysis. Am J Hum Genet 1993; 48: 7882.CrossRefGoogle Scholar
Pickens, RSvikis, DMacgue, MLabuda, M.Common genetic mechanisms in alcohol, drug, and mental disoder comorbidity. Drug Alcohol Depend 1995; 39: 129–38.CrossRefGoogle Scholar
Schuckit, MAGoodwin, DAWinokur, G.A study of alcoholism in half siblings. Am J Psychiatry 1972; 128: 1132–6.CrossRefGoogle ScholarPubMed
Smith, SO’Hara, BPérsico, A, et al. The D2 dopamine Taq B1 RFLP appears more frequently in polysubstance abusers. Arch Gen Psychiatry 1992; 49: 723–7.CrossRefGoogle ScholarPubMed
Sobell, JHeston, LSommer, S.Novel association approach for determining the genetic predisposition to schizophrenia: case-control resource and testing of a candidate gene. Am J Med Gen 1993; 48: 2835.CrossRefGoogle ScholarPubMed
Suarez, BParsian, AHampe, CTodd, RReich, TCloninger, C.Linkage desequilibria at the D2 dopamine receptor locus (DRD2) in alcoholics and Controls. Genomics 1994; 19: 1220.CrossRefGoogle ScholarPubMed
Terwilliger, JOtt, J.Handbook for human genetic linkage. Baltimore: Johns Hopkins University Press; 1994.Google Scholar
Uhl, GRPérsico, AMSmith, SS.Current excitement with dopamine receptor gene alleles in substance abuse. Arch Gen Psychiatry 1992; 49: 157–60.CrossRefGoogle ScholarPubMed
Wise, RARompre, PP.Brain dopamine and reward. Annu Rev Psychol 1989; 40: 191225.CrossRefGoogle ScholarPubMed
Yates, WRCadoret, RJTroughton, EStewart, MA.An adoption study of DSM-III-R alcohol and drug dependence severity. Drug Alcohol Depend 1996; 41: 915.CrossRefGoogle Scholar