Facteurs genetiques de l'alcoolo-dependance Revue des principales donnees de la litterature.

Alcohol Dehydrogenase/genetics; Alcoholism/genetics/psychology; Aldehyde Dehydrogenase/genetics; Comorbidity; Female; Gene Expression Regulation/genetics; Genetic Predisposition to Disease/genetics; Genotype; Humans; Male; Phenotype; Polymorphism, Genetic/genetics; Receptors, Neurotransmitter/genetics; Risk Factors; Social Environment

Abstract :

[en] INTRODUCTION: Alcohol dependence is a complex and multifactorial disease resulting both from neurobiological mechanisms and environmental factors. It is frequently associated with comorbid psychiatric disorders or with specific personality or behavioral features. Although action can be taken on the environment in order to decrease the risk of the illness, current methods used to prevent or to treat this pathology show moderate efficacy: problematic consumption of ethanol in the general population as well as relapse rates under treatment in dependent patients remain indeed very high. LITERATURE FINDINGS: It is therefore of major importance to broaden our knowledge of alcohol dependence and its comorbidities so as to improve both their prevention and treatment. In this perspective, recent progress in the field of neurosciences may contribute to achieve this goal. Precisely, genetics is a promising way benefiting from many advances in genetic epidemiology, cellular and molecular biology, neuroimaging and pharmacology. In parallel with a better understanding of the neurobiology of addictions and associated behaviors, these techniques led to the identification of brain mechanisms in which a genetic variation may influence the individual vulnerability towards alcohol dependence. Moreover, there is growing evidence that alcoholism results from the interaction of genetic and environmental factors influencing both its expression and its course. Given the fact that alcohol-dependence seems highly heritable (50 to 60% of the variance in both men and women), this review assesses the role of some of the genomic regions linked with the disease, as well as the principal variants of candidate genes identified as specifically involved in the predisposition. Polymorphisms of genes influencing alcohol metabolism, GABAergic, dopaminergic and serotonergic neurotransmission seem, indeed, at stake in the development of alcohol-dependence and its related features such as personality, behavior, impulse control or craving. In the future, a better characterization of the links between genotypes and phenotypes will probably increase our ability to treat alcoholic patients.

Disciplines :

Psychiatry

Author, co-author :

Pinto, Emmanuel ; Centre Hospitalier Universitaire de Liège - CHU > Psychiatrie et psychologie médicale

Ansseau, Marc ; Université de Liège - ULiège > Département des sciences cliniques > Psychiatrie et psychologie médicale

Language :

French

Title :

Facteurs genetiques de l'alcoolo-dependance Revue des principales donnees de la litterature.

Alternative titles :

[en] Genetic factors of alcohol-dependence

Publication date :

2009

Journal title :

Encéphale (L')

ISSN :

0013-7006

eISSN :

2589-4935

Publisher :

Editions Doin Deren et Cie, Paris, France

Volume :

Issue :

Pages :

461-9

Peer reviewed :

Peer Reviewed verified by ORBi

Available on ORBi :

since 17 February 2009

Statistics

Number of views

33 (1 by ULiège)

Number of downloads

0 (0 by ULiège)

More statistics

Scopus citations^®

Scopus citations^®
without self-citations

OpenCitations

Bibliography

Barr C.L., and Kidd K.K. Population frequencies of the A1 allele at the dopamine D2 receptor locus. Biol Psychiatry 34 (1993) 204-209
Bau C.H., Almeida S., and Hutz M.H. The TaqI A1 allele of the dopamine D2 receptor gene and alcoholism in Brazil: association and interaction with stress and harm avoidance on severity prediction. Am J Med Genet 96 (2000) 302-306
Belknap J.K., and Atkins A.L. The replicability of QTLs for murine alcohol preference drinking behavior across eight independent studies. Mamm Genome 12 (2001) 893-899
Berman S.M., Ozkaragoz T., Young R.M., et al. D2 dopamine receptor gene polymorphism discriminates two kinds of novelty seeking. Pers Individ Differ 33 (2002) 882
Blum K., Noble E.P., Sheridan P.J., et al. Allelic association of human dopamine D2 receptor gene in alcoholism. JAMA 263 (1990) 2055-2060
Bowirrat A, Oscar-Berman M. Relationship between dopaminergic neurotransmission, alcoholism, and reward deficiency syndrome. Am J Med Genet B Neuropsychiatr Genet 2005:29-37.
Chen C.C., Lu R.B., Chen Y.C., et al. Interaction between the functional polymorphisms of the alcohol-metabolism genes in protection against alcoholism. Am J Hum Genet 65 (1999) 796-807
Chen W.J., Lu M.L., Hsu Y.P., et al. Dopamine D2 receptor gene and alcoholism among four aboriginal groups and Han in Taiwan. Am J Med Genet 74 (1997) 129-136
Cloninger C.R. Neurogenetic adaptative mechanisms in alcoholism. Science (1987) 410-416
Cloninger C.R. Recent advances in family studies of alcoholism. In: Goede H.W., and Agarwal D.P. (Eds). Genetics and alcoholism (1987), Liss, New York 47-60
Comings D.E., Gade-Andavolu R., Gonzalez N., et al. The additive effect of neurotransmitter genes in pathological gambling. Clin Genet 60 (2001) 107-116
Conner B.T., Noble E.P., Berman S.M., et al. DRD2 genotypes and substance use in adolescent children of alcoholics. Drug Alcohol Depend 79 (2005) 379-387
Cools A.R., and Gingras M.A. Nijmegen high and low responders to novelty: a new tool in the search after the neurobiology of drug abuse liability. Pharmacol Biochem Behav 60 (1998) 151-159
Covault J., Gelernter J., Hesselbrock V., et al. Allelic and haplotypic association of GABRA2 with alcohol dependence. Am J Med Genet B Neuropsychiatr Genet 129 (2004) 104-109
Crabbe J.C. Genetic contribution to addiction. Annu Rev Psychol (2002) 435-462
De Haan L., Van Bruggen M., Lavalaye J., et al. Subjective experience and D2 receptor occupancy in patients with recent-onset schizophrenia treated with low-dose olanzapine or haloperidol: a randomized, double-blind study. Am J Psychiatry 160 (2003) 303-309
De Witte P., Pinto E., Ansseau M., et al. Alcohol and withdrawal: from animal research to clinical issues. Neurosci Biobehav Rev (2003) 189-197
Dick D.M., and Bierut L.J. The genetics of alcohol dependence. Curr Psychiatry Rep 8 (2006) 151-157
Dick DM, Nurnberger JR JI, Edenberg HJ et al. Suggestive linkage on chromosome 1 for a quantitative alcohol-related phenotype. Alcohol Clin Exp Res 2002;26:1453-1460.
Duan J., Sanders A.R., Molen J.E., et al. Polymorphisms in the 5'-untranslated region of the human serotonin receptor 1B (HTR1B) gene affect gene expression. Mol Psychiatry 8 (2003) 901-910
Dubertret C., Gouya L., Hanoun N., et al. The 3′ region of the DRD2 gene is involved in genetic susceptibility to schizophrenia. Schizophr Res 67 (2004) 75-85
Edenberg H.J., Dick D.M., Xuei X., et al. Variations in GABRA2, encoding the alpha 2 subunit of the GABA(A) receptor, are associated with alcohol dependence and with brain oscillations. Am J Hum Genet 74 (2004) 705-714
Edenberg H.J., and Kranzler H.R. The contribution of genetics to addiction therapy approaches. Pharmacol Ther 108 (2005) 86-93
Edenberg H.J., Xuei X., Chen H.J., et al. Association of alcohol dehydrogenase genes with alcohol dependence: a comprehensive analysis. Hum Mol Genet 15 (2006) 1539-1549
Ehlers C.L., Gilder D.A., Phillips E., et al. Genomic screen for loci associated with alcohol dependence in Mission Indians. Am J Med Genet B Neuropsychiatr Genet 129 (2004) 110-115
Enoch M.A., and Goldman D. The genetics of alcoholism and alcohol abuse. Curr Psychiatry Rep (2001) 144-151
Fehr C., Sander T., Lenzen K.P., et al. Confirmation of association of the GABRA2 gene with alcohol dependence by subtype-specific analysis. Psychiatr Genet 16 (2006) 9-17
Feinn R., Nellissery M., and Kranzler H.R. Meta-analysis of the association of a functional serotonin transporter promoter polymorphism with alcohol dependence. Am J Med Genet Neuropsychiatr Genet 133 (2005) 79-84
Foroud T., and Li T.K. Genetics of alcoholism: a review of recent studies in human and animal models. Am J Addict (1999) 261-278
Foroud T., Bucholz K.K., Edenberg H.J., et al. Linkage of an alcoholism-related severity phenotype to chromosome 16. Alcohol Clin Exp Res 22 (1998) 2035-2042
Giros B., Jaber M., Jones S.R., et al. Hyperlocomotion and indifference to cocaine and amphetamine in mice lacking the dopamine transporter. Nature 379 (1996) 606-612
Goldman D., Urbanek M., Guenther D., et al. Linkage and association of a functional DRD2 variant [Ser311Cys] and DRD2 markers to alcoholism, substance abuse and schizophrenia in Southwestern American Indians. Am J Med Genet 74 (1997) 386-394
Goodwin D.W. Alcoholism and heredity. Arch Gen Psychiatry (1979) 57-61
Gorwood P., Batel P., Adès J., et al. Serotonin transporter gene polymorphisms, alcoholism, and suicidal behavior. Biol Psychiatry 48 (2000) 259-264
Gorwood P., Lanfumey L., and Hamon M. Polymorphismes géniques de marqueurs sérotoninergiques et alcoolodépendance. Medecine/Sciences (2004) 1132-1138
Gorwood P., Limosin F., Batel P., et al. The A9 allele of the dopamine transporter gene is associated with delirium tremens and alcohol-withdrawal seizure. Biol Psychiatry 53 (2003) 85-92
Gorwood P., Schumann G., Treutlein J., et al. Psychopharmacogenetics of alcohol-dependence. In: Gorwood P., and Hamon M. (Eds). Psychopharmacogenetics (2006), Springer Science, New-York 177-202
Gorwood P. Contribution of genetics to the concept of risk status for alcohol dependence. J Soc Biol 194 (2000) 43-49
Grobin A.C., Matthews B.D., Devaud L.L., et al. The role of GABA-A receptors in the acute and chronic effects of ehanol. Psychopharmacology (1998) 2-19
Heath A.C., Bucholz K.K., Madden P.A., et al. Genetic and environmental contributions to alcohol dependence risk in a national twin sample: consistency of findings in women and men. Psychol Med 27 (1997) 1381-1396
Heath A.C. Genetic influences on alcoholism risk. A review on adoption and twin studies. Alcohol Health Res World (1995) 166-171
Hopfer C.J., Timberlake D., Haberstick B., et al. Genetic influences on quantity of alcohol consumed by adolescents and young adults. Drug Alcohol Depend 78 (2005) 187-193
Hwu H.G., and Chen C.H. Association of 5HT2A receptor gene polymorphism and alcohol abuse with behavior problems. Am J Med Genet 96 (2000) 797-800
Jonsson E.G., Cichon S., Gustavsson P., et al. Association between a promoter dopamine D2 receptor gene variant and the personality trait detachment. Biol Psychiatry 53 (2003) 577-584
Jonsson E.G., Nothen M.M., Grunhage F., et al. Polymorphisms in the dopamine D2 receptor gene and their relationships to striatal dopamine receptor density of healthy volunteers. Mol Psychiatry 4 (1999) 290-296
Kendler K.S., Davis C.G., and Kessler R.C. The familial aggregation of common psychiatric and substance use disorders in the National Comorbidity Survey: a family history study. Br J Psychiatry (1997) 541-548
Kendler K.S., Heath A.C., Neale M.C., et al. A population-based twin study of alcoholism in women. JAMA 268 (1992) 1877-1882
Kendler K.S., Neale M.C., Heath A.C., et al. A twin-family study in alcoholism in women. Am J Psychiatry 151 (1994) 707-715
Kendler K.S., Walters E., Neale M.C., et al. The structure of the genetic and environmental risk factors for six major psychiatric disorders in women. Arch Gen Psychiatry (1995) 374-383
Kono Y., Yoneda H., Sakai T., et al. Association between early-onset alcoholism and the dopamine D2 receptor gene. Am J Med Genet 74 (1997) 179-182
Lahti J., Raikkonen K., Ekelund J., et al. Novelty seeking: interaction between parental alcohol use and dopamine D4 receptor gene exon III polymorphism over 17 years. Psychiatr Genet 15 (2005) 133-139
Lappalainen J., Long J.C., Eggert M., et al. Linkage of antisocial alcoholism to the serotonin 5-HT1B receptor gene in 2 populations. Arch Gen Psychiatry 55 (1998) 989-994
Lawford B.R., Young R.M., Noble E.P., et al. The D2 dopamine receptor A1 allele and opioid dependence: Association with heroin use and response to methadone treatment. Am J Med Genet 96 (2000) 592-598
Li T.K. Pharmacogenetics of responses to alcohol and genes that influence alcohol drinking. J Stud Alcohol (2000) 5-12
Limosin F., Gorwood P., Loze J.Y., et al. Male limited association of the dopamine D2 gene Taq Ia polymorphism and alcohol dependence. Am J Med Genet 112 (2002) 343-346
Limosin F., Loze J.Y., Boni C., et al. The A9 allele of the dopamine transporter gene increases the risk of visual hallucinations during alcohol withdrawal in alcohol-dependent women. Neurosci Lett 362 (2004) 91-94
Limosin F., Loze J.Y., Dubertret C., et al. Impulsiveness as the intermediate link between the doamine D2 receptor gene and alcohol dependence. Psychiatry Genet 13 (2003) 127-129
Long J.C., Knowler W.C., Hanson R.L., et al. Evidence for genetic linkage to alcohol dependence on chromosomes 4 and 11 from an autosome-wide scan in an american indian population. Am J Med Genet B Neuropsychiatr Genet 81 (1998) 216-221
Luciano M., Zhu G., Kirk K.M., et al. Effects of dopamine receptor D4 variation on alcohol and tobacco use and on novelty seeking: multivariate linkage and association analysis. Am J Med Genet B Neuropsychiatr Genet 124 (2004) 113-123
Midanik L. Familial alcoholism and problem drinking in a national drinking practices survey. Addict Behav (1983) 133-141
Nakamura T., Matsushita S., Nishiguchi N., et al. Association of a polymorphism of the 5HT2A receptor gene promoter region with alcohol dependence. Mol Psychiatry 4 (1999) 85-88
Neumark Y.D., Friedlander Y., Durst R., et al. Alcohol dehydrogenase polymorphisms influence alcohol-elimination rates in a male Jewish population. Alcohol Clin Exp Res 28 (2004) 10-14
Neumark Y.D., Friedlander Y., Thomasson H.R., et al. Association of the ADH2*2 allele with reduced ethanol consumption in Jewish men in Israel: a pilot study. J Stud Alcohol 59 (1999) 133-139
Noble E.P., Blum K., Khalsa M.E., et al. Allelic association of the D2 dopamine receptor gene with cocaine dependence. Drug Alcohol Depend 34 (1993) 271-285
Noble E.P., Blum K., Ritchie T., et al. Allelic association of the D2 dopamine receptor gene with receptor-binding characteristics in alcoholism. Arch Gen Psychiatry 48 (1991) 648-654
Noble E.P. D2 dopamine receptor gene in psychiatric and neurologic disorders and its phenotypes. Am J Med Genet B (Neuropsychiatr Genet) 116 (2003) 103-125
Noble E.P. The D2 dopamine receptor gene: A review of association studies in alcoholism. Alcohol (1998) 33-45
Pani L., Porcella A., and Gessa G.L. The role of stress in the pathophysiology of the dopaminergic system. Mol Psychiatry 5 (2000) 14-21
Pastorelli R., Saieva C., Cerri A., et al. Genetic determinants of alcohol addiction and metabolism: a survey in Italy. Alcohol Clin Exp Res 25 (2001) 221-227
Pinto E., Reggers J., Gorwood P., et al. Implication of the A1 allele of the DRD2 in alcohol craving. Am J Med Genet B Neuropsychiatr Genet 138B (2005) 37
Pohjalainen T., Rinne J.O., Nagren K., et al. The A1 allele of the human D2 dopamine receptor gene predicts low D2 receptor availability in healthy volunteers. Mol Psychiatry 3 (1998) 256-260
Porjesz B., Almasy L., Edenberg H.J., et al. Linkage disequilibrium between the beta frequency of the human EEG and a GABAA receptor gene locus. Proc Natl Acad Sci U S A 99 (2002) 3729-3733
Porjesz B., Rangaswamy M., Kamarajan C., et al. The utility of neurophysiological markers in the study of alcoholism. Clin Neurophysiol 116 (2005) 993-1018
Prescott C.A., Aggen S.H., and Kendler K.S. Sex differences in the sources of genetic liability to alcohol abuse and dependence in a population-based sample of U.S. twins. Alcohol Clin Exp Res 23 (1999) 1136-1144
Preuss U.W., Soyka M., Bahlmann M., et al. Serotonin transporter gene regulatory region polymorphism (5-HTTLPR), [3H]paroxetine binding in healthy control subjects and alcohol-dependent patients and their relationships to impulsivity. Psychiatry Res 96 (2000) 51-61
Reich T., Cloninger C.R., Van Eerrdewegh P., et al. Secular trends in the transmission of alcoholism. Alcohol Clin Exp Res 12 (1988) 458-464
Reich T., Edenberg H.J., Goate A., et al. Genome-wide search for genes affecting the risk for alcohol dependence. Am J Med Genet B Neuropsychiatr Genet 81 (1998) 207-215
Rogers G., Joyce P., Mulder R., et al. Association of a duplicated repeat polymorphism in the 5′-untranslated region of the DRD4 gene with novelty seeking. Am J Med Genet B Neuropsychiatr Genet 126 (2004) 98
Saccone N.L., Kwon J.M., Corbett J., et al. A genome screen of maximum number of drinks as an alcoholism phenotype. Am J Med Genet 96 (2000) 632-637
Saccone S., Saccone N., Neuman R., et al. Genetic analysis of the maximum drinks phenotype. BMC Genetics 6 (2005) S124
Sander T., Harms H., Dufeu P., et al. Serotonin transporter gene variants in alcohol-dependent subjects with dissocial personality disorder. Biol Psychiatry 43 (1998) 908-912
Sander T., Harms H., Lesch K.P., et al. Association analysis of a regulatory variation of the serotonin transporter gene with severe alcohol dependence. Alcohol Clin Exp Res 21 (1997) 1356-1359
Sander T., Harms H., Podschus J., et al. Allelic association of a dopamine transporter gene polymorphism in alcohol dependence with withdrawal seizures or delirium. Biol Psychiatry (1997) 299-304
Schindler K.M., Pato M.T., Dourado A., et al. Association and linkage disequilibrium between a functional polymorphism of the dopamine-2 receptor gene and schizophrenia in a genetically homogeneous Portuguese population. Mol Psychiatry 7 (2002) 1002-1005
Schmidt L.G., Harms H., Kuhn S., et al. Modification of alcohol withdrawal by the A9 allele of the dopamine transporter gene. Am J Psychiatry 155 (1998) 474-478
Schuckit M., Mazzanti C., Smith T.L., et al. Selective genotyping for the role of 5-HT2A, 5-HT2C, and GABAα6 receptors and the serotonin transporter in the level of response to alcohol: a pilot study. Biol Psychiatry 5 (1999) 647-651
Schuckit M.A. Vulnerability factors for alcoholism. In: Davis K.L., Charney D.S., Coyle J.T., et al. (Eds). Neuropsychopharmacology. The fifth generation of progress (2002), Lippincott Williams and Wilkins, Philadelphia 1399-1411
Shibuya A., and Yoshida A. Genotypes of alcohol-metabolizing enzymes in Japanes with alcohol liver diseases: a strong association of the usual caucasian-type aldehyde dehydrogenase gene (ALDH 2) with the disease. Am J Hum Genet (1988) 744-748
Sluyter F., Hof M., Ellenbroek B.A., et al. Genetic, sex, and early environmental effects on the voluntary alcohol intake in Wistar rats. Pharmacol Biochem Behav 67 (2000) 801-808
Soyka M., Preuss U.W., Koller G., et al. Association of 5-HT1B receptor gene and antisocial behavior in alcoholism. J Neural Transm 111 (2004) 101-109
Spitz M.R., Shi H., Yang F., et al. Case-control study of the D2 dopamine receptor gene and smoking status in lung cancer patients. J Natl Cancer Inst 90 (1998) 358-363
Suhara T., Yasuno F., Sudo Y., et al. Dopamine D2 receptors in the insular cortex and the personality trait of novelty seeking. Neuroimage 13 (2001) 891-895
Tupala E., and Tiihonen J. Dopamine and alcoholism: neurobiological basis of ethanol abuse. Prog Neuropsychopharmacol Biol Psychiatry 28 (2004) 1221-1247
Volkow N.D., Wang G.J., Fowler J.S., et al. Brain DA D2 receptors predict reinforcing effects of stimulants in humans: replication study. Synapse (New York, N Y) 46 (2002) 79-82
Whitfield J.B. Meta-analysis of the effects of alcohol dehydrogenase genotype on alcohol dependence and alcoholic liver disease. Alcohol Alcohol (1997) 613-619
Williams J.T., Begleiter H., Porjesz B., et al. Joint multipoint linkage analysis of multivariate qualitative and quantitative traits. II. Alcoholism and event-related potentials. Am J Hum Genet 65 (1999) 1148-1160
Xu K., Lichtermann D., Lipsky R.H., et al. Association of specific haplotypes of D2 receptor gene with vulnerability to heroin dependence in 2 distinct populations. Arch Gen Psychiatry 61 (2004) 597-606
Young R.M., Lawford B.R., Nutting A., et al. Advances in molecular genetics and the prevention and treatment of substance misuse: Implications of association studies of the A1 allele of the D2 dopamine receptor gene. Addict Behav 29 (2004) 1275-1294