Human Genetics

, Volume 132, Issue 3, pp 347–358 | Cite as

A large-scale meta-analysis of the association between the ANKK1/DRD2 Taq1A polymorphism and alcohol dependence

  • Fan Wang
  • Arthur Simen
  • Albert Arias
  • Qun-Wei Lu
  • Huiping ZhangEmail author
Original Investigation


Alcohol dependence (AD) is a common neuropsychiatric disorder with high heritability. A number of studies have analyzed the association between the Taq1A polymorphism (located in the gene cluster ANKK1/DRD2) and AD. In the present study, we conducted a large-scale meta-analysis to confirm the association between the Taq1A polymorphism and the risk for AD in over 18,000 subjects included in 61 case–control studies that were published up to August 2012. Our meta-analysis demonstrated both allelic and genotypic association between the Taq1A polymorphism and AD susceptibility [allelic: P(Z) = 1.1 × 10−5, OR = 1.19; genotypic: P(Z) = 3.2 × 10−5, OR = 1.24]. The association remained significant after adjustment for publication bias using the trim and fill method. Sensitivity analysis showed that the effect size of the Taq1A polymorphism on AD risk was moderate and not influenced by any individual study. The pooled odds ratio from published studies decreased with the year of publication, but stabilized after the year 2001. Subgroup analysis indicated that publication bias could be influenced by racial ancestry. In summary, this large-scale meta-analysis confirmed the association between the Taq1A polymorphism and AD. Future studies are required to investigate the functional significance of the ANKK1/DRD2 Taq1A polymorphism in AD.


Publication Bias Alcohol Dependence Fill Method DRD2 Gene Asian Subgroup 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



This study was supported by the National Institute of Health (NIH) Grants K99/R00 DA022891 and the grant from the Alcoholic Beverage Medical Research Foundation (ABMRF).

Conflict of interest

The authors have no conflict of interest to report.

Supplementary material

439_2012_1251_MOESM1_ESM.doc (938 kb)
Supplementary material 1 (DOC 938 kb)


  1. Amadeo S, Abbar M, Fourcade ML, Waksman G, Leroux MG, Madec A, Selin M, Champiat JC, Brethome A, Leclaire Y et al (1993) D2 dopamine receptor gene and alcoholism. J Psychiatr Res 27:173–179PubMedCrossRefGoogle Scholar
  2. Amadeo S, Noble EP, Fourcade-Amadeo ML, Tetaria C, Brugiroux MF, Nicolas L, Deparis X, Elbaz A, Zhang X, Ritchie T, Martin PV, Mallet J (2000) Association of D2 dopamine receptor and alcohol dehydrogenase 2 genes with Polynesian alcoholics. Eur Psychiatry 15:97–102PubMedCrossRefGoogle Scholar
  3. Anghelescu I, Germeyer S, Muller MJ, Klawe C, Singer P, Dahmen N, Wetzel H, Himmerich H, Szegedi A (2001) No association between the dopamine d2 receptor taqi a1 allele and earlier age of onset of alcohol dependence according to different specified criteria. Alcohol Clin Exp Res 25:805–809PubMedCrossRefGoogle Scholar
  4. Arinami T, Itokawa M, Komiyama T, Mitsushio H, Mori H, Mifune H, Hamaguchi H, Toru M (1993) Association between severity of alcoholism and the A1 allele of the dopamine D2 receptor gene TaqI A RFLP in Japanese. Biol Psychiatry 33:108–114PubMedCrossRefGoogle Scholar
  5. Bau CH, Almeida S, Hutz MH (2000) 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 96:302–306PubMedCrossRefGoogle Scholar
  6. Berggren U, Fahlke C, Aronsson E, Karanti A, Eriksson M, Blennow K, Thelle D, Zetterberg H, Balldin J (2006) The taqI DRD2 A1 allele is associated with alcohol-dependence although its effect size is small. Alcohol Alcohol 41:479–485PubMedCrossRefGoogle Scholar
  7. Bhaskar LV, Thangaraj K, Non AL, Singh L, Rao VR (2010) Population-based case–control study of DRD2 gene polymorphisms and alcoholism. J Addict Dis 29:475–480PubMedCrossRefGoogle Scholar
  8. Blum K, Noble EP, Sheridan PJ, Montgomery A, Ritchie T, Jagadeeswaran P, Nogami H, Briggs AH, Cohn JB (1990) Allelic association of human dopamine D2 receptor gene in alcoholism. JAMA 263:2055–2060PubMedCrossRefGoogle Scholar
  9. Blum K, Noble EP, Sheridan PJ, Finley O, Montgomery A, Ritchie T, Ozkaragoz T, Fitch RJ, Sadlack F, Sheffield D et al (1991) Association of the A1 allele of the D2 dopamine receptor gene with severe alcoholism. Alcohol 8:409–416PubMedCrossRefGoogle Scholar
  10. Bolos AM, Dean M, Lucas-Derse S, Ramsburg M, Brown GL, Goldman D (1990) Population and pedigree studies reveal a lack of association between the dopamine D2 receptor gene and alcoholism. JAMA 264:3156–3160PubMedCrossRefGoogle Scholar
  11. Bontempi S, Fiorentini C, Busi C, Guerra N, Spano P, Missale C (2007) Identification and characterization of two nuclear factor-kappaB sites in the regulatory region of the dopamine D2 receptor. Endocrinology 148:2563–2570PubMedCrossRefGoogle Scholar
  12. Chen CH, Chien SH, Hwu HG (1996) Lack of association between TaqI A1 allele of dopamine D2 receptor gene and alcohol-use disorders in atayal natives of Taiwan. Am J Med Genet 67:488–490PubMedCrossRefGoogle Scholar
  13. Chen WJ, Lu ML, Hsu YP, Chen CC, Yu JM, Cheng AT (1997) Dopamine D2 receptor gene and alcoholism among four aboriginal groups and Han in Taiwan. Am J Med Genet 74:129–136PubMedCrossRefGoogle Scholar
  14. Comings DE (1998) Why different rules are required for polygenic inheritance: lessons from studies of the DRD2 gene. Alcohol 16:61–70PubMedCrossRefGoogle Scholar
  15. Comings DE, Comings BG, Muhleman D, Dietz G, Shahbahrami B, Tast D, Knell E, Kocsis P, Baumgarten R, Kovacs BW et al (1991) The dopamine D2 receptor locus as a modifying gene in neuropsychiatric disorders. JAMA 266:1793–1800PubMedCrossRefGoogle Scholar
  16. Comings DE, Muhleman D, Ahn C, Gysin R, Flanagan SD (1994) The dopamine D2 receptor gene: a genetic risk factor in substance abuse. Drug Alcohol Depend 34:175–180PubMedCrossRefGoogle Scholar
  17. Cook BL, Wang ZW, Crowe RR, Hauser R, Freimer M (1992) Alcoholism and the D2 receptor gene. Alcohol Clin Exp Res 16:806–809PubMedCrossRefGoogle Scholar
  18. Cruz C, Camarena B, Mejia JM, Paez F, Eroza V, Ramon De La Fuente J, Kershenobich D, Nicolini H (1995) The dopamine D2 receptor gene TaqI A1 polymorphism and alcoholism in a Mexican population. Arch Med Res 26:421–6Google Scholar
  19. DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7:177–188PubMedCrossRefGoogle Scholar
  20. Dick DM, Wang JC, Plunkett J, Aliev F, Hinrichs A, Bertelsen S, Budde JP, Goldstein EL, Kaplan D, Edenberg HJ, Nurnberger J Jr, Hesselbrock V, Schuckit M, Kuperman S, Tischfield J, Porjesz B, Begleiter H, Bierut LJ, Goate A (2007) Family-based association analyses of alcohol dependence phenotypes across DRD2 and neighboring gene ANKK1. Alcohol Clin Exp Res 31:1645–1653PubMedCrossRefGoogle Scholar
  21. Duval S, Tweedie R (2000) A nonparametric “trim and fill” method of accounting for publication bias in meta-analysis. J Am Stat Assoc 89–98Google Scholar
  22. Egger M, Smith GD, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315:629–634PubMedCrossRefGoogle Scholar
  23. Finckh U, von Widdern O, Giraldo-Velasquez M, Podschus J, Dufeu P, Sander T, Harms H, Schmidt LG, Rommelspacher H, Rolfs A (1996) No association of the structural dopamine D2 receptor (DRD2) variant 311Cys with alcoholism. Alcohol Clin Exp Res 20:528–532PubMedCrossRefGoogle Scholar
  24. Fiorentini C, Guerra N, Facchetti M, Finardi A, Tiberio L, Schiaffonati L, Spano P, Missale C (2002) Nerve growth factor regulates dopamine D(2) receptor expression in prolactinoma cell lines via p75(NGFR)-mediated activation of nuclear factor-kappaB. Mol Endocrinol 16:353–366PubMedCrossRefGoogle Scholar
  25. Foley PF, Loh EW, Innes DJ, Williams SM, Tannenberg AE, Harper CG, Dodd PR (2004) Association studies of neurotransmitter gene polymorphisms in alcoholic Caucasians. Ann N Y Acad Sci 1025:39–46PubMedCrossRefGoogle Scholar
  26. Freire MT, Marques FZ, Hutz MH, Bau CH (2006) Polymorphisms in the DBH and DRD2 gene regions and smoking behavior. Eur Arch Psychiatry Clin Neurosci 256:93–97PubMedCrossRefGoogle Scholar
  27. Galbraith R (1988) Graphical display of estimates having differing standard errors. Technometrics 271–281Google Scholar
  28. Geijer T, Neiman J, Rydberg U, Gyllander A, Jonsson E, Sedvall G, Valverius P, Terenius L (1994) Dopamine D2-receptor gene polymorphisms in Scandinavian chronic alcoholics. Eur Arch Psychiatry Clin Neurosci 244:26–32PubMedCrossRefGoogle Scholar
  29. Gelernter J, Kranzler H (1999) D2 dopamine receptor gene (DRD2) allele and haplotype frequencies in alcohol dependent and control subjects: no association with phenotype or severity of phenotype. Neuropsychopharmacology 20:640–649PubMedCrossRefGoogle Scholar
  30. Gelernter J, O’Malley S, Risch N, Kranzler HR, Krystal J, Merikangas K, Kennedy JL, Kidd KK (1991) No association between an allele at the D2 dopamine receptor gene (DRD2) and alcoholism. JAMA 266:1801–1807PubMedCrossRefGoogle Scholar
  31. Gelernter J, Yu Y, Weiss R, Brady K, Panhuysen C, Yang BZ, Kranzler HR, Farrer L (2006) Haplotype spanning TTC12 and ANKK1, flanked by the DRD2 and NCAM1 loci, is strongly associated to nicotine dependence in two distinct American populations. Hum Mol Genet 15:3498–3507PubMedCrossRefGoogle Scholar
  32. Ghosh J, Pradhan S, Mittal B (2012) Identification of a novel ANKK1 and other dopaminergic (DRD2 and DBH) gene variants in migraine susceptibility. Neuromol Med [Epub ahead of print] PubMed PMID: 22875483Google Scholar
  33. Goldman D, Dean M, Brown GL, Bolos AM, Tokola R, Virkkunen M, Linnoila M (1992) D2 dopamine receptor genotype and cerebrospinal fluid homovanillic acid, 5-hydroxyindoleacetic acid and 3-methoxy-4-hydroxyphenylglycol in alcoholics in Finland and the United States. Acta Psychiatr Scand 86:351–357PubMedCrossRefGoogle Scholar
  34. Goldman D, Brown GL, Albaugh B, Robin R, Goodson S, Trunzo M, Akhtar L, Lucas-Derse S, Long J, Linnoila M et al (1993) DRD2 dopamine receptor genotype, linkage disequilibrium, and alcoholism in American Indians and other populations. Alcohol Clin Exp Res 17:199–204PubMedCrossRefGoogle Scholar
  35. Goldman D, Urbanek M, Guenther D, Robin R, Long JC (1997) 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 74:386–394PubMedCrossRefGoogle Scholar
  36. Gonzalez S, Rangel-Barajas C, Peper M, Lorenzo R, Moreno E, Ciruela F, Borycz J, Ortiz J, Lluis C, Franco R, McCormick PJ, Volkow ND, Rubinstein M, Floran B, Ferre S (2012) Dopamine D4 receptor, but not the ADHD-associated D4.7 variant, forms functional heteromers with the dopamine D2S receptor in the brain. Mol Psychiatry 17:650–662PubMedCrossRefGoogle Scholar
  37. Gorwood P, Batel P, Gouya L, Courtois F, Feingold J, Ades J (2000a) Reappraisal of the association between the DRD2 gene, alcoholism and addiction. Eur Psychiatry 15:90–96PubMedCrossRefGoogle Scholar
  38. Gorwood P, Bellivier F, Ades J, Leboyer M (2000b) The DRD2 gene and the risk for alcohol dependence in bipolar patients. Eur Psychiatry 15:103–108PubMedCrossRefGoogle Scholar
  39. Heinz A, Sander T, Harms H, Finckh U, Kuhn S, Dufeu P, Dettling M, Graf K, Rolfs A, Rommelspacher H, Schmidt LG (1996) Lack of allelic association of dopamine D1 and D2 (TaqIA) receptor gene polymorphisms with reduced dopaminergic sensitivity to alcoholism. Alcohol Clin Exp Res 20:1109–1113PubMedCrossRefGoogle Scholar
  40. Hietala J, Pohjalainen T, Heikkila-Kallio U, West C, Salaspuro M, Syvalahti E (1997) Allelic association between D2 but not D1 dopamine receptor gene and alcoholism in Finland. Psychiatr Genet 7:19–25PubMedCrossRefGoogle Scholar
  41. Hirvonen M, Laakso A, Nagren K, Rinne JO, Pohjalainen T, Hietala J (2004) C957T polymorphism of the dopamine D2 receptor (DRD2) gene affects striatal DRD2 availability in vivo. Mol Psychiatry 9:1060–1061PubMedCrossRefGoogle Scholar
  42. Huang SY, Lin WW, Wan FJ, Chang AJ, Ko HC, Wang TJ, Wu PL, Lu RB (2007) Monoamine oxidase-A polymorphisms might modify the association between the dopamine D2 receptor gene and alcohol dependence. J Psychiatry Neurosci 32:185–192PubMedGoogle Scholar
  43. Huang W, Payne TJ, Ma JZ, Beuten J, Dupont RT, Inohara N, Li MD (2009) Significant association of ANKK1 and detection of a functional polymorphism with nicotine dependence in an African-American sample. Neuropsychopharmacology 34:319–330PubMedCrossRefGoogle Scholar
  44. Hummel M, Unterwald EM (2002) D1 dopamine receptor: a putative neurochemical and behavioral link to cocaine action. J Cell Physiol 191:17–27PubMedCrossRefGoogle Scholar
  45. Ishiguro H, Arinami T, Saito T, Akazawa S, Enomoto M, Mitushio H, Fujishiro H, Tada K, Akimoto Y, Mifune H, Shioduka S, Hamaguchi H, Toru M, Shibuya H (1998) Association study between the -141C Ins/Del and TaqI A polymorphisms of the dopamine D2 receptor gene and alcoholism. Alcohol Clin Exp Res 22:845–848PubMedGoogle Scholar
  46. Joe KH, Kim DJ, Park BL, Yoon S, Lee HK, Kim TS, Cheon YH, Gwon DH, Cho SN, Lee HW, Namgung S, Shin HD (2008) Genetic association of DRD2 polymorphisms with anxiety scores among alcohol-dependent patients. Biochem Biophys Res Commun 371:591–595PubMedCrossRefGoogle Scholar
  47. Karaoguz MY, Cosar B, Sahin FI (2004) Lack of association between TaqIA RFLP of the Dopamine D2 receptor gene and alcoholism in Type 2 Turkish Alcoholics. Gene Genomics 26:149–154Google Scholar
  48. Kasiakogia-Worlley K, McQuillin A, Lydall GJ, Patel S, Kottalgi G, Gunwardena P, Cherian R, Rao H, Hillman A, Gobikrishnan N, Douglas E, Qureshi SY, Jauhar S, Ball D, Okane A, Owens L, Dedman A, Sharp SI, Kandaswamy R, Guerrini I, Thomson AD, Smith I, Dar K, Morgan MY, Gurling HM (2011) Lack of allelic association between markers at the DRD2 and ANKK1 gene loci with the alcohol-dependence syndrome and criminal activity. Psychiatr Genet 21:323–324PubMedCrossRefGoogle Scholar
  49. Kienast T, Heinz A (2006) Dopamine and the diseased brain. CNS Neurol Disord: Drug Targets 5:109–131CrossRefGoogle Scholar
  50. Konishi T, Calvillo M, Leng AS, Lin KM, Wan YJ (2004a) Polymorphisms of the dopamine D2 receptor, serotonin transporter, and GABA(A) receptor beta(3) subunit genes and alcoholism in Mexican-Americans. Alcohol 32:45–52PubMedCrossRefGoogle Scholar
  51. Konishi T, Luo HR, Calvillo M, Mayo MS, Lin KM, Wan YJ (2004b) ADH1B*1, ADH1C*2, DRD2 (-141C Ins), and 5-HTTLPR are associated with alcoholism in Mexican American men living in Los Angeles. Alcohol Clin Exp Res 28:1145–1152PubMedCrossRefGoogle Scholar
  52. Kono Y, Yoneda H, Sakai T, Nonomura Y, Inayama Y, Koh J, Sakai J, Inada Y, Imamichi H, Asaba H (1997) Association between early-onset alcoholism and the dopamine D2 receptor gene. Am J Med Genet 74:179–182PubMedCrossRefGoogle Scholar
  53. Kovanen L, Saarikoski ST, Haukka J, Pirkola S, Aromaa A, Lonnqvist J, Partonen T (2010) Circadian clock gene polymorphisms in alcohol use disorders and alcohol consumption. Alcohol Alcohol 45:303–311PubMedCrossRefGoogle Scholar
  54. Kraschewski A, Reese J, Anghelescu I, Winterer G, Schmidt LG, Gallinat J, Finckh U, Rommelspacher H, Wernicke C (2009) Association of the dopamine D2 receptor gene with alcohol dependence: haplotypes and subgroups of alcoholics as key factors for understanding receptor function. Pharmacogenet Genomics 19:513–527PubMedCrossRefGoogle Scholar
  55. Landgren S, Berglund K, Jerlhag E, Fahlke C, Balldin J, Berggren U, Zetterberg H, Blennow K, Engel JA (2011) Reward-related genes and personality traits in alcohol-dependent individuals: a pilot case control study. Neuropsychobiology 64:38–46PubMedCrossRefGoogle Scholar
  56. Lawford BR, Young RM, Rowell JA, Gibson JN, Feeney GF, Ritchie TL, Syndulko K, Noble EP (1997) Association of the D2 dopamine receptor A1 allele with alcoholism: medical severity of alcoholism and type of controls. Biol Psychiatry 41:386–393PubMedCrossRefGoogle Scholar
  57. Le Foll B, Gallo A, Le Strat Y, Lu L, Gorwood P (2009) Genetics of dopamine receptors and drug addiction: a comprehensive review. Behav Pharmacol 20:1–17PubMedCrossRefGoogle Scholar
  58. Lee MS, Lee KJ, Kwak DI (1997) No association between the dopamine D2 receptor gene and Korean alcoholism. Psychiatr Genet 7:93–95PubMedCrossRefGoogle Scholar
  59. Limosin F, Gorwood P, Loze JY, Dubertret C, Gouya L, Deybach JC, Ades J (2002) Male limited association of the dopamine receptor D2 gene TaqI a polymorphism and alcohol dependence. Am J Med Genet 112:343–346PubMedCrossRefGoogle Scholar
  60. Lu RB, Ko HC, Chang FM, Castiglione CM, Schoolfield G, Pakstis AJ, Kidd JR, Kidd KK (1996) No association between alcoholism and multiple polymorphisms at the dopamine D2 receptor gene (DRD2) in three distinct Taiwanese populations. Biol Psychiatry 39:419–429PubMedCrossRefGoogle Scholar
  61. Lu RB, Lee JF, Ko HC, Lin WW (2001) Dopamine D2 receptor gene (DRD2) is associated with alcoholism with conduct disorder. Alcohol Clin Exp Res 25:177–184PubMedCrossRefGoogle Scholar
  62. Lu RB, Lee JF, Huang SY, Lee SY, Chang YH, Kuo PH, Chen SL, Chen SH, Chu CH, Lin WW, Wu PL, Ko HC (2012) Interaction between ALDH2*1*1 and DRD2/ANKK1 TaqI A1A1 genes may be associated with antisocial personality disorder not co-morbid with alcoholism. Addict Biol 17:865–874PubMedCrossRefGoogle Scholar
  63. Matsushita S, Muramatsu T, Murayama M, Nakane J, Higuchi S (2001) Alcoholism, ALDH2*2 allele and the A1 allele of the dopamine D2 receptor gene: an association study. Psychiatry Res 104:19–26PubMedCrossRefGoogle Scholar
  64. Mota NR, Rovaris DL, Bertuzzi GP, Contini V, Vitola ES, Grevet EH, Roman T, Callegari-Jacques SM, Hutz MH, Bau CH (2012) DRD2/DRD4 heteromerization may influence genetic susceptibility to alcohol dependence. Mol Psychiatry [Epub ahead of print] PubMed PMID: 22565782Google Scholar
  65. Munafo MR, Matheson IJ, Flint J (2007) Association of the DRD2 gene Taq1A polymorphism and alcoholism: a meta-analysis of case-control studies and evidence of publication bias. Mol Psychiatry 12:454–461PubMedGoogle Scholar
  66. Namkoong K, Cheon KA, Kim JW, Jun JY, Lee JY (2008) Association study of dopamine D2, D4 receptor gene, GABAA receptor beta subunit gene, serotonin transporter gene polymorphism with children of alcoholics in Korea: a preliminary study. Alcohol 42:77–81PubMedCrossRefGoogle Scholar
  67. Neiswanger K, Hill SY, Kaplan BB (1995) Association and linkage studies of the TAQI A1 allele at the dopamine D2 receptor gene in samples of female and male alcoholics. Am J Med Genet 60:267–271PubMedCrossRefGoogle Scholar
  68. Neville MJ, Johnstone EC, Walton RT (2004) Identification and characterization of ANKK1: a novel kinase gene closely linked to DRD2 on chromosome band 11q23.1. Hum Mutat 23:540–545PubMedCrossRefGoogle Scholar
  69. Noble EP, Blum K, Ritchie T, Montgomery A, Sheridan PJ (1991) Allelic association of the D2 dopamine receptor gene with receptor-binding characteristics in alcoholism. Arch Gen Psychiatry 48:648–654PubMedCrossRefGoogle Scholar
  70. Noble EP, Syndulko K, Fitch RJ, Ritchie T, Bohlman MC, Guth P, Sheridan PJ, Montgomery A, Heinzmann C, Sparkes RS et al (1994) D2 dopamine receptor TaqI A alleles in medically ill alcoholic and nonalcoholic patients. Alcohol Alcohol 29:729–744PubMedGoogle Scholar
  71. Ovchinnikov IV, Druzina E, Ovtchinnikova O, Zagorovskaya T, Nebarakova T, Anokhina IP (1999) Polymorphism of dopamine D2 and D4 receptor genes and Slavic-surnamed alcoholic patients. Addict Biol 4:399–404PubMedCrossRefGoogle Scholar
  72. Parsian A, Todd RD, Devor EJ, O’Malley KL, Suarez BK, Reich T, Cloninger CR (1991) Alcoholism and alleles of the human D2 dopamine receptor locus. Studies of association and linkage. Arch Gen Psychiatry 48:655–663PubMedCrossRefGoogle Scholar
  73. Pastorelli R, Bardazzi G, Saieva C, Cerri A, Gestri D, Allamani A, Airoldi L, Palli D (2001) Genetic determinants of alcohol addiction and metabolism: a survey in Italy. Alcohol Clin Exp Res 25:221–227PubMedCrossRefGoogle Scholar
  74. Pohjalainen T, Rinne JO, Nagren K, Lehikoinen P, Anttila K, Syvalahti EK, Hietala J (1998) The A1 allele of the human D2 dopamine receptor gene predicts low D2 receptor availability in healthy volunteers. Mol Psychiatry 3:256–260PubMedCrossRefGoogle Scholar
  75. Ponce G, Hoenicka J, Rodriguez-Jimenez R, Gozalo A, Jimenez M, Monasor R, Aragues M, Rubio G, Jimenez-Arriero MA, Ramos JA, Palomo T (2004) IDRD2 TaqIA polymorphism is associated with urinary homovanillic acid levels in a sample of Spanish male alcoholic patients. Neurotox Res 6:373–377PubMedCrossRefGoogle Scholar
  76. Ponce G, Hoenicka J, Jimenez-Arriero MA, Rodriguez-Jimenez R, Aragues M, Martin-Sune N, Huertas E, Palomo T (2008) DRD2 and ANKK1 genotype in alcohol-dependent patients with psychopathic traits: association and interaction study. Br J Psychiatry 193:121–125PubMedCrossRefGoogle Scholar
  77. Prasad P, Ambekar A, Vaswani M (2010) Dopamine D2 receptor polymorphisms and susceptibility to alcohol dependence in Indian males: a preliminary study. BMC Med Genet 11:24PubMedCrossRefGoogle Scholar
  78. Prescott CA, Kendler KS (1999) Genetic and environmental contributions to alcohol abuse and dependence in a population-based sample of male twins. Am J Psychiatry 156:34–40PubMedGoogle Scholar
  79. Sakai JT, Hopfer CJ, Hartman C, Haberstick BC, Smolen A, Corley RP, Stallings MC, Young SE, Timberlake D, Hewitt JK, Crowley TJ (2007) Test of association between TaqIA A1 allele and alcohol use disorder phenotypes in a sample of adolescent patients with serious substance and behavioral problems. Drug Alcohol Depend 88:130–137PubMedCrossRefGoogle Scholar
  80. Samochowiec J, Ladehoff M, Pelz J, Smolka M, Schmidt LG, Rommelspacher H, Finckh U (2000) Predominant influence of the 3′-region of dopamine D2 receptor gene (DRD2) on the clinical phenotype in German alcoholics. Pharmacogenetics 10:471–475PubMedCrossRefGoogle Scholar
  81. Samochowiec J, Kucharska-Mazur J, Grzywacz A, Pelka-Wysiecka J, Mak M, Samochowiec A, Bienkowski P (2008) Genetics of Lesch’s typology of alcoholism. Prog Neuropsychopharmacol Biol Psychiatry 32:423–427PubMedCrossRefGoogle Scholar
  82. Sander T, Harms H, Podschus J, Finckh U, Nickel B, Rolfs A, Rommelspacher H, Schmidt LG (1995) Dopamine D1, D2 and D3 receptor genes in alcohol dependence. Psychiatr Genet 5:171–176PubMedCrossRefGoogle Scholar
  83. Sander T, Ladehoff M, Samochowiec J, Finckh U, Rommelspacher H, Schmidt LG (1999) Lack of an allelic association between polymorphisms of the dopamine D2 receptor gene and alcohol dependence in the German population. Alcohol Clin Exp Res 23:578–581PubMedCrossRefGoogle Scholar
  84. Schellekens AF, Franke B, Ellenbroek B, Cools A, de Jong CA, Buitelaar JK, Verkes RJ (2012) Reduced Dopamine receptor sensitivity as an intermediate phenotype in alcohol dependence and the role of the COMT Val158Met and DRD2 Taq1A genotypes. Arch Gen Psychiatry 69:339–348PubMedCrossRefGoogle Scholar
  85. Shaikh KJ, Naveen D, Sherrin T, Murthy A, Thennarasu K, Anand A, Benegal V, Jain S (2001) Polymorphisms at the DRD2 locus in early-onset alcohol dependence in the Indian population. Addict Biol 6:331–335PubMedCrossRefGoogle Scholar
  86. Smith L, Watson M, Gates S, Ball D, Foxcroft D (2008) Meta-analysis of the association of the Taq1A polymorphism with the risk of alcohol dependency: a HuGE gene–disease association review. Am J Epidemiol 167:125–138PubMedCrossRefGoogle Scholar
  87. Wang TJ, Huang SY, Lin WW, Lo HY, Wu PL, Wang YS, Wu YS, Ko HC, Shih JC, Lu RB (2007) Possible interaction between MAOA and DRD2 genes associated with antisocial alcoholism among Han Chinese men in Taiwan. Prog Neuropsychopharmacol Biol Psychiatry 31:108–114PubMedCrossRefGoogle Scholar
  88. Wise RA, Rompre PP (1989) Brain dopamine and reward. Annu Rev Psychol 40:191–225PubMedCrossRefGoogle Scholar
  89. Wu CY, Wu YS, Lee JF, Huang SY, Yu L, Ko HC, Lu RB (2008) The association between DRD2/ANKK1, 5-HTTLPR gene, and specific personality trait on antisocial alcoholism among Han Chinese in Taiwan. Am J Med Genet B Neuropsychiatr Genet 147B:447–453PubMedCrossRefGoogle Scholar
  90. Yang BZ, Kranzler HR, Zhao H, Gruen JR, Luo X, Gelernter J (2007) Association of haplotypic variants in DRD2, ANKK1, TTC12 and NCAM1 to alcohol dependence in independent case control and family samples. Hum Mol Genet 16:2844–2853PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  • Fan Wang
    • 1
    • 2
  • Arthur Simen
    • 1
    • 3
  • Albert Arias
    • 1
    • 2
  • Qun-Wei Lu
    • 4
  • Huiping Zhang
    • 1
    • 2
    Email author
  1. 1.Department of PsychiatryYale University School of MedicineWest HavenUSA
  2. 2.VA Connecticut Healthcare SystemWest HavenUSA
  3. 3.Merck Research LaboratoriesNorth WalesUSA
  4. 4.College of Life Science and Technology, Center for Human Genome ResearchHuazhong University of Science and TechnologyWuhanChina

Personalised recommendations