Hostname: page-component-586b7cd67f-tf8b9 Total loading time: 0 Render date: 2024-11-28T14:47:23.788Z Has data issue: false hasContentIssue false
  • English
  • Français

Reappraisal of the association between the DRD2 gene, alcoholism and addiction

Published online by Cambridge University Press:  16 April 2020

P. Gorwood ,
P. Batel ,
L. Gouya ,
F. Courtois ,
J. Feingold  and
J. Adès
P. Gorwood*
Affiliation:
Laboratory of genetics epidemiology (INSERM Unit 155), Paris, France Psychiatric department, Biochemistry laboratory, Hospital Louis Mourier, 178 rue des Renouillers, 92701, Colombes, France
P. Batel
Affiliation:
Unité de Traitement Ambulatoire des Malades Alcooliques,’ ‘Centre de Transfusion Sanguine,’ Hospital Beaujon, Paris, France
L. Gouya
Affiliation:
Biochemistry laboratory (Fédération de biologie Moléculaire, INSERM Unité 409), Hospital Louis Mourier, 178 rue des Renouillers, 92701, Colombes, France
F. Courtois
Affiliation:
‘Centre de Transfusion Sanguine,’ Hospital Beaujon (Assistance Publique-Hôpitaux de Paris), Paris, France
J. Feingold
Affiliation:
Laboratory of genetics epidemiology (INSERM Unit 155), Paris, France
J. Adès
Affiliation:
Psychiatric department, Biochemistry laboratory, Hospital Louis Mourier, 178 rue des Renouillers, 92701, Colombes, France
*
*Correspondence and reprints: Philip Gorwood M.D., Ph.D. (CNRS UMR 7593), Service de psychiatrie adulte du Professeur Adès, Hôpital Louis Mourier, 178, rue des Renouillers, 92701 Colombes cedex, France
Get access

Summary

We analysed the impact of the TaqI A1 allele of the D2 dopamine receptor gene on the risk for alcoholism, trying to depict three explanations frequently proposed to explain discrepancies in association and linkage studies: that the A1 allele may act as a marker rather than as a vulnerability factor, that stratification biases and unevaluated controls may explain positive results, and that the A1 allele is modifying the phenotype rather than increasing the risk for alcoholism. We thus tested another (dinucleotide STRP) marker within the DRD2 gene, selected a new homogenous sample of 113 alcoholic patients and 49 unaffected controls strictly matched for ethnic origins, and systematically assessed both samples with a semi-structured interview to detect (in both samples) alcohol dependence, but also such related traits as specificities of complications.

The frequency of the A1 allele was not significantly different between alcoholics and controls but when comparing different subgroups of alcoholics, the A1 allele was significantly more frequent in alcoholic patients with somatic complications (OR = 3.00, CI[1.37-6.62]), social and professional complications (OR = 2.72, CI[1.25-5.90]), or with co-morbid dependence (OR = 2.88, 95% IC [1.16-7.15]). The association for co-morbid dependence and somatic complications was also positive when taking into consideration both STRP and TaqIA polymorphisms.

The A1 allele does not increase the risk for alcoholism per se in our sample, but may be involved in a related trait which is partially dependent on the diagnosis of alcoholism, through a disequilibrium with another close mutation.

Keywords

A1 allelecomplicationsdependencegenetics
Type
Original Article
Information
European Psychiatry , Volume 15 , Issue 2 , March 2000 , pp. 90 - 96
Copyright
Copyright © Éditions scientifiques et médicales Elsevier SAS 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

Amadeo, SAbbar, MFourcade, M.LWacksman, GLeroux, MMadec, A et al. D2 dopamine receptor gene and alcoholism. J Psychiat Res 2 1993 173–179CrossRefGoogle Scholar
Barr, C.LKidd, K.KPopulation frequencies of the A1 allele at the dopamine D2 receptor locus. Biol Psychiatry 31 1993 285Google Scholar
Blum, KNoble, ESheridan, PMontgomey, ARitchie, TOzkaragoz, T et al. Genetic predisposition in alcoholism : association of the D2 dopamine receptor Taq1 B1 RFLP with severe alcoholics. Alcohol 10 1993 59–67CrossRefGoogle ScholarPubMed
Blum, KSheridan, PWood, RBracermann, EChen, TComings, DDopamine D2 receptor gene variants: association and linkage studies in impulsive-addictive-compulsive behaviour. Pharmacogenetics 5 1995 121–141CrossRefGoogle ScholarPubMed
Bohman, MSome genetic aspects of alcoholism and criminality : A population of adoptees. Arch Gen Psychiatry 35 1978 269–276CrossRefGoogle ScholarPubMed
Bolos, ADean, MLucs-Derse, SRamsburg, MBrown, GGoldman, DPopulation and pedigree studies reveal a lack of association between the dopamine D2 receptor gene and alcoholism. JAMA 264 1990 3156–3160CrossRefGoogle ScholarPubMed
Cloninger, CD2 dopamine receptor gene is associated but not linked with alcoholism. JAMA 266 1991 1833–1834CrossRefGoogle Scholar
Comings, DComings, BDonn Muhleman, M.S et al. The dopamine D2 receptor locus as a modifying gene in neuropsychiatric disorders. JAMA 266 1991 1793–1800CrossRefGoogle ScholarPubMed
Cook, CGurling, HThe D2 dopamine receptor gene and alcoholism: a genetic effect on the liability of alcoholism. J R Soc M 87 1994 400–402Google 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 169 1996 243–248CrossRefGoogle ScholarPubMed
Cotton, N.SThe familial incidence of alcoholism. A review. J Stud Alcohol 40 1979 89–116CrossRefGoogle ScholarPubMed
Coughlin, SBenichou, JWeed, DAttributable risk estimation in case-control studies. Epidemiol Rev 16 1994 51–64CrossRefGoogle ScholarPubMed
Cruz, CCamarena, BMejia, JPaez, FEroza, VRamon, D.ELa Fuente, R et al. The dopamine D2 receptor gene TaqI A1 polymorphism and alcoholism in a Mexican population. Arch Med Res 26 1995 421–426Google Scholar
Debrettes, BBerlin, ILaurent, CLépine, J.PMallet, JPuech, AThe dopamine D2 receptor gene TaqI A polymorphism is not associated with novelty seeking, harm avoidance and reward dependence in healthy subjects. Eur Psychiatry 13 1998 427–430CrossRefGoogle Scholar
Finckh, UGiraldo Velasquez, MPelz, JOtto, GSander, TSchmidt, L et al. Dopamine D2 receptor gene (DRD2): haplotypes in caucasians. Gene 179 1996 251–255CrossRefGoogle ScholarPubMed
Gelertner, JO'Malley, SRisch, NKranzler, HKrystal, JMerikangas, K et al. No association between an allele at the D2 dopamine receptor gene (D2) and alcoholism. JAMA 266 1991 1801–1807Google Scholar
Goldman, DBrown, G.LAlbaugh, BRobin, RGoodson, STrunzo, M et al. D2 dopamine receptor genotype, linkage disequilibrium, and alcoholism in American Indians and other populations. Alcohol Clin Exp Res 17 1993 199–204CrossRefGoogle ScholarPubMed
Goldman, DUrbanek, MGuenther, DRobin, RLong, J.CLinkage 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 74 1997 386–3943.0.CO;2-N>CrossRefGoogle Scholar
Gorwood, PAdès, JFeingold, JAre genes coding for dopamine receptors implicated in alcoholism? Eur Psychiatry 9 1994 63–69CrossRefGoogle Scholar
Gorwood, PGenetic association studies in behavioral neuroscience.Cruzio, WGerlai, RMolecular genetic techniques for behavioural neuroscience. 1999 Amsterdam: ElsevierGoogle Scholar
Grandy, D.KZhang, YCivelli, OPCR detection of the TaqA RFLP at the DRD2 locus. Hum Mol Genet 2 1993 2197CrossRefGoogle ScholarPubMed
Hauge, X.YGrandy, D.KEubanks, J.HEvans, G.ACivelli, OLitt, MDetection and characterisation of additional DNA polymorphisms in the dopamine D2 receptor gene. Genomics 10 1991 527–530CrossRefGoogle Scholar
Koob, G.FDrugs of abuse: anatomy, pharmacology and function of reward pathways. Trends Pharmacol Sci 13 1992 177–184CrossRefGoogle ScholarPubMed
Lawford, BYoung, RRowell, JGibson, JFeeney, GRitchie, T et al. Association of the D2 dopamine receptor A1 allele with alcoholism: medical severity of alcoholism and type of controls. Biol Psychiatry 41 1997 386–393CrossRefGoogle ScholarPubMed
Loparev, V.NCartas, M.AMonken, CVelpandi, ASrinivajan, AAn efficient and simple method of DNA extraction from whole blood and cell lines to identify infectious agents. J Virol Methods 34 1991 105–112CrossRefGoogle ScholarPubMed
Neiswanger, KHill, S.YKaplan, B.BAssociation and linkage studies of the TAQ1A1 allele at the dopamine D2 receptor gene in samples of female and male alcoholics. Am J Med Gen 60 1995 267–271CrossRefGoogle Scholar
Neiswanger, KKaplan, B.BHill, S.YWhat can the D2/alcoholism story teach us about association studies in psychiatric genetics ? Am J Med Gen 60 1995 272–275CrossRefGoogle ScholarPubMed
Noble, ESyndulko, KFitch, JRitchie, TBohlman, MGuth, P et al. D2 dopamine receptor Taq1 A alleles in medically ill alcoholic and nonalcoholic patients. Alcohol Alcohol 29 1994 729–744Google Scholar
Noble, E.PThe D2 dopamine receptor gene: a review of association studies in alcoholism. Behav Genet 23 1993 119–129CrossRefGoogle ScholarPubMed
Noble, E.PAlcoholism and the dopaminergic system: a review. Addict Biology 1 1996 333–348CrossRefGoogle ScholarPubMed
Noble, E.PBlum, KKhalsa, MRitchie, TMontgomery, AWood, R et al. Allelic association of the D2 dopamine receptor gene with cocaine dependence. Drug Alcohol Depend 33 1993 271–285CrossRefGoogle ScholarPubMed
Nurnberger, J.IBlehar, M.CKaufmann, C.AYork-Cooler, CSimpson, S.GHarkavy-Friedman, J et al. Diagnostic Interview for Genetic Studies: rational, unique features, and training. Arch Gen Psychiatry 51 1994 849–862CrossRefGoogle Scholar
Parsian, ATodd, RDevor, EO'Malley, KSuarez, BReich, T et al. Alcoholism and alleles of the human D2 dopamine receptor locus. Arch Gen Psychiatry 48 1991 655–663CrossRefGoogle ScholarPubMed
Pato, CMacciardi, FPato, MVerga, MKennedy, HReview of the putative association of the DRD2 and alcoholism: a meta-analysis. Am J Hum Genet 48 1993 78–82CrossRefGoogle ScholarPubMed
Pickens, RSvikis, DMacgue, MLabuda, MCommon genetic mechanisms in alcohol, drug, and mental disorder comorbidity. Drug Alcohol Depend 39 1995 129–138CrossRefGoogle ScholarPubMed
Schuckit, M.AGoodwin, D.AWinokur, GA study of alcoholism in half siblings. Am J Psychiatry 128 1972 1132–1136CrossRefGoogle ScholarPubMed
Smith, SO'Hara, BPersico, A et al. The D2 dopamine Taq B1 RFLP appears more frequently in polysubstance abusers. Arch Gen Psychiatry 49 1992 723–727CrossRefGoogle ScholarPubMed
Sobell, JHeston, LSommer, SNovel association approach for determining the genetic predisposition to schizophrenia: case-control resource and testing of a candidate gene. Am J Med Gen 48 1993 28–35CrossRefGoogle ScholarPubMed
Suarez, BParsian, AHampe, CTodd, RReich, TCloninger, CLinkage desequilibria at the D2 dopamine receptor locus (DRD2) in alcoholics and controls. Genomics 19 1994 12–20CrossRefGoogle ScholarPubMed
Terwilliger, JOtt, JHandbook for human genetic linkage. 1994 Baltimore: Johns Hopkins University PressGoogle Scholar
Uhl, G.RPersico, A.MSmith, S.SCurrent excitement with dopamine receptor gene alleles in substance abuse. Arch Gen Psychiatry 49 1992 157–160CrossRefGoogle ScholarPubMed
Wise, R.ARompre, P.PBrain dopamine and reward. Annu Rev Psychol 40 1989 191–225CrossRefGoogle ScholarPubMed
Yates, W.RCadoret, R.JTroughton, EStewart, M.AAn adoption study of DSM-III-R alcohol and drug dependence severity. Drug Alcohol Depend 41 1996 9–15CrossRefGoogle Scholar
Submit a response

Comments

No Comments have been published for this article.