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Association of D2 dopamine receptor and alcohol dehydrogenase 2 genes with Polynesian alcoholics

Published online by Cambridge University Press:  16 April 2020

S. Amadéo*
Affiliation:
Service de Psychiatrie Adulte, Hopital Vaiami, Papeete Tahiti, Polynésie, Française Laboratoire de Génétique Moléculaire de la Neurotransmission et des Processus Neurodégénératifs, CNRS, Batiment CERVI, Hôpital de la Pitié, Salpêtrière, Paris, France
E.P. Noble
Affiliation:
UCLA Neuropsychiatric Institute and Brain Research Institute, Los AngelesCA, USA
M.L. Fourcade-Amadéo
Affiliation:
CHT de Mamao et Centre de Transfusion Sanguine, Papeete Tahiti, Polynésie, Française
C. Tetaria
Affiliation:
CHT de Mamao et Centre de Transfusion Sanguine, Papeete Tahiti, Polynésie, Française
M.F. Brugiroux
Affiliation:
Service d'Alcoologie et Toxicomanie, Papeete Tahiti, Polynésie, Française
L. Nicolas
Affiliation:
Institut Territorial de Recherches Médicales Louis Malardé, Papeete Tahiti, Polynésie, Française
X. Deparis
Affiliation:
Institut Territorial de Recherches Médicales Louis Malardé, Papeete Tahiti, Polynésie, Française
A. Elbaz
Affiliation:
Inserm, Pointe à Pitre, Guadeloupe
X. Zhang
Affiliation:
UCLA Neuropsychiatric Institute and Brain Research Institute, Los AngelesCA, USA
T. Ritchie
Affiliation:
UCLA Neuropsychiatric Institute and Brain Research Institute, Los AngelesCA, USA
P.V. Martin
Affiliation:
Institut Territorial de Recherches Médicales Louis Malardé, Papeete Tahiti, Polynésie, Française
J. Mallet
Affiliation:
Laboratoire de Génétique Moléculaire de la Neurotransmission et des Processus Neurodégénératifs, CNRS, Batiment CERVI, Hôpital de la Pitié, Salpêtrière, Paris, France
*
*Correspondence and reprints
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Summary

Alleles of the D2 dopamine receptor (DRD2) and the alcohol dehydrogenase 2 (ADH2) genes were determined in 69 French Polynesian alcoholic patients and 57 controls matched for racial origin. Three racial groups were studied: pure Polynesians (PP), Polynesians mixed with Caucasian (PCA) ancestry and Polynesians mixed with Chinese (PCH) ancestry. DRD2 A1 allele frequencies in the alcoholics compared to their controls in these groups were: PP,.26 vs .32 (P = .69); PCA, .44 vs .35 (P = .46); PCH, .40 vs 0.39 (P = .88). ADH2 1 allele frequencies in alcoholics compared to their controls groups were: PP, .56 vs .62 (P = .66); PCA, .75 vs .56 (P = .09); PCH, .78 vs .32 (P = .009). In the PCA group, the combination of the DRD2 A1 genotypes and the ADH2 1 homozygotes was strongly associated with alcoholism (P = .0027). This preliminary study shows the importance of ascertaining racial ancestry in molecular genetic association studies. Moreover, it suggests that a combination of genes are involved in susceptibility to the development of alcoholism.

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Original Article
Copyright
Copyright © Éditions scientifiques et médicales Elsevier SAS 2000

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References

Amadéo, SFourcade, M.LAbbar, MLeroux, M.GMadec, ASelin, M et al. D2 Dopamine receptor gene and alcoolism. J Psychiatr Res 27 1993 73–17910.1016/0022-3956(93)90005-MCrossRefGoogle Scholar
Arinami, TItokawa, MKomiyama, MMitsushio, HMori, HMifune, H et al. Association between severity of alcoholism and the A1 allele of the Dopamine D2 Receptor gene TaqIA RFLP in Japanese. Biol Psychiatry 33 1993 108–11410.1016/0006-3223(93)90309-2CrossRefGoogle Scholar
Barr, C.LKidd, K.KPopulation frequencies of the A1 allele at the dopamine D2 receptor locus. Biol Psychiatry 34 1993 204–20910.1016/0006-3223(93)90073-MCrossRefGoogle ScholarPubMed
Bennion, L.JLi, T.KAlcohol metabolism in American Indians and whites. N Engl J M 294 1976 9–1310.1056/NEJM197601012940103CrossRefGoogle ScholarPubMed
Blum, KNoble, E.PScheridan, P.JMontgomery, ARitchie, TJagadeeswaran, P et al. Allelic association of human dopamine D2 receptor gene in alcoholism. JAMA 263 1990 2055–206010.1001/jama.1990.03440150063027CrossRefGoogle ScholarPubMed
Blum, KNoble, E.PSheridan, P.JFinley, OMontgomery, ARitchie, T et al. Association of the A1 Allele of the D2 Dopamine eceptor gene with severe alcoholism. Alcohol 8 1991 409–41610.1016/0741-8329(91)90693-QCrossRefGoogle Scholar
Blum, KSheridan, P.JWood, R.CBraverman, E.RChen, IComings, D.EDopamine D2 receptor gene variants: association and linkage studies in impulsive-addictive-compulsive behavior. Pharmacogenetics 5 1995 121–14110.1097/00008571-199506000-00001CrossRefGoogle Scholar
Bolos, A.MDean, MLucas-Derse, SRamsburg, MBrown, G.LGoldman, DPopulation and pedigree studies reveal a lack of association between the dopamine D2 receptor gene and alcoholism. JAMA 264 1990 3156–316010.1001/jama.1990.03450240058040CrossRefGoogle ScholarPubMed
Bosron, W.FLi, T.KGenetic polymorphism of human liver alcohol and aldehyde dehydrogenase, and their relationship to alcohol metabolism and alcoholism. Hepatology 6 1986 502–51010.1002/hep.1840060330CrossRefGoogle ScholarPubMed
Chen, C.HChien, S.HHwu, H.GLack of association between TaqI A1 allele of dopamine D2 receptor gene and alcohol-use disorder in Atayal natives of Taiwan. Am J Med Genet Neuropsychiatric Genetics 67 1996 488–49010.1002/(SICI)1096-8628(19960920)67:5<488::AID-AJMG10>3.0.CO;2-J3.0.CO;2-J>CrossRefGoogle ScholarPubMed
Chen, C.HLoh, E.WHwu, H.GCheng, T.AAlcohol dehydrogenase and aldehyde dehydrogenase genotypes and alcoholism among Taiwanese aborigines. Biol Psychiatry 41 1997 703–70910.1016/S0006-3223(96)00072-8CrossRefGoogle ScholarPubMed
Cloninger, C.RD2 dopamine receptor gene is associated but not linked with alcoholism. JAMA 266 1991 1833–183410.1001/jama.1991.03470130113040CrossRefGoogle Scholar
Coga, Semi-structured assessment for the genetics of alcoholism. National Institute of Alcohol Abuse and Alcoholism. Washington, DC 1993Google Scholar
Comings, D.EComings, B.GMuhleman, DDietz, GShahbahrami, BTast, D et al. The dopamine D2 receptor locus as a modifying gene in neuropsychiatric disorders. JAMA 266 1991 1793–180010.1001/jama.1991.03470130073032CrossRefGoogle ScholarPubMed
Cook, B.LWang, Z.WCrowe, R.RHauser, RFreimer, MAlcoholism and the D2 receptor gene. Alcohol Clin Exp Res 16 1992 806–80910.1111/j.1530-0277.1992.tb00683.xCrossRefGoogle ScholarPubMed
Cook, C.CGurling, HThe D2 dopamine receptor gene and alcoholism: a genetic effect on the liability for alcoholism. J R Soc M 87 1994 400–402Google ScholarPubMed
Edenberg, H.JForoud, TKoller, D.LGoate, ARice, JVanEerdewegh, P et al. A family-based analysis of the association of the dopamine D2 receptor (DRD2) with alcoholism. Alcohol Clin Exp Res 22 1998 505–51210.1111/j.1530-0277.1998.tb03680.xCrossRefGoogle ScholarPubMed
Finckh, UVon Widdern, OGiraldo-Velasquez, MPodschus, JDufeu, PSander, T et al. No association of the structural dopamine D2 receptor (DRD2) variant (311) Cys with alcoholism. Alcohol Clin Exp Res 20 1996 528–53210.1111/j.1530-0277.1996.tb01087.xCrossRefGoogle Scholar
Gejman, P.VRam, AGerlenter, JFriedman, ECao, QPickar, D et al. No structural mutation in the dopamine D2 receptor gene in alcoholism or schizophrenia. JAMA 271 1994 204–20810.1001/jama.1994.03510270050038CrossRefGoogle ScholarPubMed
Gelernter, JO'Malley, SRisch, NKranzler, H.RKrystal, JMerikangas, K et al. No association between an allele of the D2 dopamine receptor gene (DRD2) and alcoholism. JAMA 266 1991 1801–180710.1001/jama.1991.03470130081033CrossRefGoogle ScholarPubMed
Gelernter, JGoldman, DRisch, NThe A1 allele at the D2 dopamine receptor gene and alcoholism: A reappraisal. JAMA 269 1993 1673–167710.1001/jama.1993.03500130087038CrossRefGoogle ScholarPubMed
Goldman, DBrown, G.LAlbaugh, BRobin, RGoodson, STrunzo, M et al. DRD2 dopamine receptor genotype, linkage desequilibrium, and alcoholism in American Indians and other populations. Alcohol Clin Exp Res 17 1993 199–20410.1111/j.1530-0277.1993.tb00749.xCrossRefGoogle Scholar
Gorwood, PAdes, JFeingold, JAre genes coding for dopamine receptors implicated in alcoholism? Eur Psychiatry 9 1994 63–6910.1017/S0924933800001772CrossRefGoogle Scholar
Grandy, D.KLitt, MAllen, LBunzow, J.RMarchionni, MMakam, H et al. The human dopamine D2 receptor gene is located on chromosome 11 at q22q23 and identifies a Taq I RFLP. Am J Hum Genet 45 1989 778–785Google Scholar
Grandy, D.KZhang, YCivelli, OPCR detection of the TaqA RFLP at the DRD2 locus. Hum Mol Genet 2 1993 219710.1093/hmg/2.12.2197-aCrossRefGoogle ScholarPubMed
Hietala, JPohjalainen, THeikkilä-Kalio West, CSalaspuro, MSyvälahti, EAllelic association between D2 but not D1 dopamine receptor gene and alcoholism in Finland. Psychiatr Genet 7 1997 19–2510.1097/00041444-199700710-00003CrossRefGoogle Scholar
Kono, YYoneda, HSakai, TNonomura, YInayama, YKoh, J et al. Association between early-onset alcoholism and the dopamine D2 receptor gene. Am J Med Genet 74 1997 179–18210.1002/(SICI)1096-8628(19970418)74:2<179::AID-AJMG13>3.0.CO;2-F3.0.CO;2-F>CrossRefGoogle ScholarPubMed
Kopun, MPropping, PThe kinetics of ethanol absorption and elimination in twins and supplementary repetitive experiments in singleton subjects Eur J Clin Pharmacol 11 1977 337–43310.1007/BF00566530CrossRefGoogle ScholarPubMed
Lawford, B.RYoung, R.M.C.DRowell, J.AQualichefski, JFletcher, BSyndulko, K et al. Bromocriptine in the treatment of alcoholics with the D2 dopamine receptor A1 allele. Nat M 1 1995 337–34110.1038/nm0495-337CrossRefGoogle ScholarPubMed
Lawford, B.RYoung, R.M.C.DRowell, J.AQualichefski, JFletcher, BSyndulko, K et al. Association of the D2 dopamine receptor A1 allele with alcoholism: Medical severity of alcoholism and type of controls. Biol Psychiatry 41 1997 386–39310.1016/S0006-3223(96)00478-7CrossRefGoogle ScholarPubMed
Lu, R.BChang, F.MCastiglione, C.MSchoolfield, GPaksis, A.JKidd, J.R et al. No association between alcoholism and multiple polymorphisms at the dopamine D2 receptor gene (DRD2) in three distinct Taiwanese populations. Biol Psychiatry 39 1996 419–429CrossRefGoogle ScholarPubMed
Martin, N.GPerl, JOakeshott, J.GGibson, J.BStarmer, G.AWilks, A.VA twin study of ethanol metabolism. Behav Genet 15 1985 93–10910.1007/BF01065891CrossRefGoogle ScholarPubMed
Nakamura, KSuwaki, HMatsuo, YIkawa, YMiyatake, RIwahashi, KAssociation between alcoholics and the genotypes of ALDH2, ADH2, ADH3 as well as P-450E1. Jpn J Alcohol Stud Drug Depend 36 1995 33–42Google Scholar
Neiswanger, KHill, S.YKaplan, B.BAssociation and linkage studies of the Taq A1 allele at the DRD2 receptor gene in samples of female and male alcoholics. Am J Med Genet 60 1995 267–27110.1002/ajmg.1320600402CrossRefGoogle ScholarPubMed
Neumark, Y.DFriedlander, YThomasson, H.RLi, T.KAssociation of the ADH2*2 allele with reduced ethanol consumption in Jewish men in Israel: a pilot study. J Stud Alcohol 59 1998 133–13910.15288/jsa.1998.59.133CrossRefGoogle ScholarPubMed
Noble, E.PThe D2 dopamine receptor gene : a review of association studies in alcoholism. Behav Genet 23 1993 119–129CrossRefGoogle ScholarPubMed
Noble, E.PBlum, KAlcoholism and the D2 dopamine receptor gene [letter]. JAMA 270 1993 154710.1001/jama.270.13.1547CrossRefGoogle ScholarPubMed
Noble, E.PThe D2 dopamine receptor gene: a review of association studies in alcoholism and phenotypes. Alcohol 5 1998 1–13Google Scholar
Noble, E.PBlum, KMontgomery, ASheridan, P.JAllelic association of the D2 dopamine receptor gene with receptor-binding characteristics in alcoholism. Arch Gen Psychiatry 48 1991 648–65410.1001/archpsyc.1991.01810310066012CrossRefGoogle ScholarPubMed
Noble, E.PNoble, R.ERitchie, TSyndulko, KBohlman, M.CNoble, L.A et al. D2 dopamine receptor gene and obesity. Int J Eat Disord 14 1994 205–21710.1002/1098-108X(199404)15:3<205::AID-EAT2260150303>3.0.CO;2-P3.0.CO;2-P>CrossRefGoogle Scholar
Noble, E.PSyndulko, KFitch, R.JRitchie, TBohlman, CGuth, P et al. D2 dopamine receptor Taq A alleles in medically ill alcoholic and nonalcoholic patients. Alcohol 29 1994 729–744Google ScholarPubMed
O'Hara, B.FSmith, S.SBird, GPersico, A.MSuarez, B.KCutting, G.R et al. Dopamine D2 receptor RFLPs, haplotypes and their association with substance use in Black and Caucasian research volunteers. Hum Her 43 1993 209–21810.1159/000154133CrossRefGoogle ScholarPubMed
Parsian, ATodd, R.DDevor, E.JO'Malley, KSuarez, B.KReich, T et al. Alcoholism and alleles of the human D2 dopamine receptor locus: studies of association and linkage. Arch Gen Psychiatry 48 1991 655–663CrossRefGoogle ScholarPubMed
Pato, C.NMacciadi, FPato, M.TVerga, MKennedy, J.LReview of the putative association of dopamine receptor and alcoholism: a meta-analysis. Am J Med Genet 48 1993 78–82CrossRefGoogle ScholarPubMed
Pohjalainen, TRinne, JNågren, KLehikoinen, PAnttila, KSyvälahti, E.K.G et al. The A1 allele of the human D2 dopamine receptor gene predicts low D2 dopamine receptor availability in healtly individuals. Mol Psychiatry 3 1998 256–26010.1038/sj.mp.4000350CrossRefGoogle Scholar
Shibuya, AYasunami Myoshida, AGenotypes of alcohol dehydrogenase and aldehyde dehydrogenase loci in Japanese alcohol flushers and nonflushers. Hum Genet 82 1989 14–16CrossRefGoogle ScholarPubMed
Shen, Y.CFan, J.HEdenberg, H.JLi, T.KCui, Y.HWang, Y.F et al. Polymorphism of ADH and ALDH genes among four ethnic groups in China and effects upon the risk for alcoholism. Alcohol Clin Exp Res 21 1997 1272–127710.1111/j.1530-0277.1997.tb04448.xCrossRefGoogle ScholarPubMed
Smith, MGenetics of human alcohol and aldehyde dehydrogenase. Adv Hum Genet 15 1986 249–290Google Scholar
Suarez, B.KParsian, AHampe, C.LTodd, R.DReich, TCloninger, C.RLinkage disequilibria at the D2 dopamine receptor in alcoholics and controls. Genomics 19 1994 12–20CrossRefGoogle ScholarPubMed
Takeshita, TMao, X.QMasimoto, KThe contribution of polymorphism in the alcohol dehydrogenase beta submit to alcohol sensitivity in a Japanese population. Hum Genet 97 1996 409–41310.1007/BF02267057CrossRefGoogle Scholar
Thomasson, H.REdenberg, H.JCrabb, D.WMai, X.LJerome, R.ELi, T.K et al. Alcohol and aldehyde dehydrogenase genotypes and alcoholism in Chinese men. Am J Hum Genet 48 1991 677–681Google ScholarPubMed
Turner, EEwing, JShilling, PSmith, T.LIrwin, MSchuckit, M et al. Lack of association between an RFLP near the D2 dopamine receptor gene and severe alcoholism. Biol Psychiatr 31 1992 285–29010.1016/0006-3223(92)90052-2CrossRefGoogle ScholarPubMed
Turner, ALawrence, JChih-Hui Chen, ACook, CGurling, HFrequency of the A1/A2 alleles of the D2 dopamine receptor (DRD2) gene in a British, Caucasian control group screened to exclude alcoholism and heavy drinking. Addict Biol 2 1997 207–213CrossRefGoogle Scholar
Uhl, RBlum, KNoble, E.PSmith, S.SSubstance abuse vulnerability and DRD2 gene. Trends Neurosci 16 1993 83–8810.1016/0166-2236(93)90128-9CrossRefGoogle Scholar
Wagner, J.GWilkinson, P.KSedman, A.JKay, D.RWeidler, D.JElimination of alcohol from human blood. J Pharm Sci 65 1976 152–154CrossRefGoogle ScholarPubMed
Xu, YCarr, L.GBosron, WLi, T.KEdenberg, H.JGenotyping of human alcohol dehydrogenase at the ADH2 and ADH3 loci following DNA sequence amplification. Genomics 2 1988 209–21410.1016/0888-7543(88)90004-3CrossRefGoogle ScholarPubMed
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