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Neurotoxicity Research

, Volume 6, Issue 5, pp 373–377 | Cite as

DRD2 TaqIA polymorphism is associated with urinary homovanillic acid levels in a sample of spanish male alcoholic patients

  • G. Ponce
  • J. Hoenicka
  • R. Rodríguez-jiménez
  • A. Gozalo
  • M. Jimenéz
  • R. Monasor
  • M. Aragüés
  • G. Rubio
  • M. A. Jiménez-arriero
  • J. A. Ramos
  • T. Palomo
Article

Abstract

TheTaqIA1 allele of the dopamine receptor gene D2 (DRD2) has been associated with alcoholism, as well as with other addictive behaviours. The exact nature of how the presence of this allele can be a vulnerability factor in the development of alcoholism remains unclear. In this study we found that the presence in theDRD2 genotype of theTaqIA1 allele in Spanish alcoholics is associated with higher levels of urine homovanillic acid (HVA) when compared to patients homozygous for theTaqIA2 allele.

A sample of 142 Spanish male alcoholic patients was split into 2 groups on the basis of the presence or absence of the A1 allele in their genotype. The urine sample was analyzed by high performance liquid cromatography (HPLC), and the concentration of homovanillic acid (HVA), 5-hydroxyin-doleacetic acid (5-HIAA) and vanilylmandelic acid (VMA) was determined. We found a statistical difference in the concentration of HVA between the groups, that suggests this polymorphism could be related to the variance of urine HVA levels.

Keywords

Alcoholism DRD2 homovanillic acid (HVA) TaqIA polymorphism 

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References

  1. Babor TF, M Hofmann, FK DelBoca, V Hesselbrock, RE Meyer, ZS Dolinsky and B Rounsaville (1992) Types of alcoholics: I.Evidence for an empirically derived typology based on indicators of vulnerability and severity. Arch. Gen. Psychiatry 49, 599–608.Google Scholar
  2. Benjamin D, ER Grant and LA Pohorecky (1993) Naltrexone reverses ethanol-induced dopamine release in the nucleus accumbens in awake, freely moving rats.Brain Res. 621, 137–140.PubMedCrossRefGoogle Scholar
  3. Blum K, EP Noble, PJ Sheridan, A Montgomery, T Ritchie, P Jagadeeswaran, H Nogami, AH Briggs and JB Cohn (1990) Allelic association of human dopamine D2 receptor gene in alcoholism.JAMA 263, 2055–2060.PubMedCrossRefGoogle Scholar
  4. Blum K, PJ Sheridan, RC Wood, ER Braverman, TJH Chen and DE Comings (1995) Dopamine D2 receptor gene variants: association and linkage studies in impulsive-addictive-compulsive behaviour.Pharmacogenetics 5, 121–141.PubMedCrossRefGoogle Scholar
  5. Cloninger CR (1991) D2 dopamine receptor gene is associated but not linked with alcoholism.JAMA 266, 1833–1834.PubMedCrossRefGoogle Scholar
  6. Cloninger R, S Sigvardson, S Gilligan, A von Knorring, T Reich and M Bohman (1988) Genetic heterogeneity and the classification of alcoholism.Adv. Alcohol. Subst. Abuse 7, 3–17.PubMedGoogle Scholar
  7. Comings DE, D Muhleman, C Ahn, R Gysin and SD Flanagan (1994) The dopamine D2 receptor gene, a genetic risk factor in substance abuse.Drug Alcohol Depend. 34, 175–180.PubMedCrossRefGoogle Scholar
  8. Comings DE, RJ Rosenthal, HR Lesieur, LJ Rugle, D Muhleman, C Chiu, G Dietz and D Muhleman (1996) A study of the dopamine D2 receptor gene in pathological gambling.Pharmacogenetics 6, 223–234.PubMedCrossRefGoogle Scholar
  9. Cook BL, ZW Wang, RR Crowe, R Hauser and M Freimer (1992) Alcoholism and the D2 receptor gene.Alcohol. Clin. Exp. Res. 16, 806–809.PubMedCrossRefGoogle Scholar
  10. Di Chiara G and A Imperato (1988) Drug abused by humans preferentially increase synaptic dopamine concentration in the mesolimbic system of freely moving rats.Proc. Natl. Acad. Sci. USA 85, 52–74.CrossRefGoogle Scholar
  11. Duan J, MS Wainwright, JM Comeron, N Saitou, AR Sanders, J Gelernter and PV Gejman (2003) Synonymous mutations in the human dopamine receptor D2 (DRD2) affect mRNA stability and synthesis of the receptor.Hum. Mol. Genetics 12, 205–216CrossRefGoogle Scholar
  12. Gabbay FH, CC Duncan, G Bird, GR Uhl and AF Mirsky (1996) D2 dopamine receptor Ta q 1A genotypic differences in event-related brain potentials, In Problems of Drug Dependence 1995 (Harris LS, Ed.) (NIDA Research Monograph 162: Rockville, MD, USA), p 129.Google Scholar
  13. Goldman D, M Dean, GL Brown, AM Bolos, R Tokola, M Virkkunen and M Linnoila (1992) D2 dopamine receptor genotype and cerebrospinal fluid homovanillic acid, 5- hydroxyin-doleacetic acid and 3-methoxy-4-hydroxyphenylglycol in alcoholics in Finland and the United States.Acta Psychiatr. Scand. 86, 351–357.PubMedCrossRefGoogle Scholar
  14. Goodwin DW (1985) Genetic Determinants of Alcoholism (McGraw Hill: New York) pp 55–70.Google Scholar
  15. Hietala J, T Pohjalainen, U Heikkila-Kallio, C West, M Salaspuro and E Syvälahti (1997) Allelic association between D2 but not D1 dopamine receptor gene and alcoholism in Finland.Psychiatr. Genet. 7, 19–25.PubMedCrossRefGoogle Scholar
  16. Hill SY, J Locke, N Zezza, B Kaplan, K Neiswanger, SR Steinhauer, G Wipprecht and J Xu (1998) Genetic association between reduced P300 amplitude and the DRD2 dopamine receptor A1 allele in children at high risk for alcoholism.Biol. Psychiatry 43, 40–51.PubMedCrossRefGoogle Scholar
  17. Jönsson E, G Sedvall, S Brené, JP Gustavsson, T Geijer, L Terenius, MA Crocq, L Lannfelt, A Tylec, P Sokoloff, JC Schwartz and FA Wiesel (1996) Dopamine-related genes and their relationships to monoamine metabolites in CSF.Biol. Psychiatr. 40, 1032–1043.CrossRefGoogle Scholar
  18. Koob GF and FE Bloom (1988) Cellular and molecular mechanisms of drug dependence.Science 242, 715–23.PubMedCrossRefGoogle Scholar
  19. Lawford BR, RM Young, JA Rowell, J Qualichefski, BH Fletcher, K Syndulko, T Ritchie and EP Noble (1995) Bromocriptine in the treatment of alcoholics with the D2 dopamine receptor A1 allele.Nat. Med. 1, 337–341.PubMedCrossRefGoogle Scholar
  20. Lehmann J and SZ Langer (1983) The striatal cholinergic interneu-ron, synaptic target of dopaminergic terminals?Neuroscience 10, 1105–1120.PubMedCrossRefGoogle Scholar
  21. Miyake H, K Nagashima, K Onigata, T Nagashima, Y Takano and A Morikawa (1999) Allelic variations of the D2 dopamine receptor gene in children with idiopathic short stature.J. Hum. Genet. 44, 26–29.PubMedCrossRefGoogle Scholar
  22. Noble EP (2000) Addiction and its reward process through polymorphisms of the D2 dopamine receptor gene, a review.Eur. Psychiatry 15, 79–89.PubMedCrossRefGoogle Scholar
  23. Noble EP (2003) D2 dopamine receptor gene in psychiatric and neurological disorders and its phenotypes.Am. J. Med. Genet. 116 (Suppl. 1), 103–125.CrossRefGoogle Scholar
  24. Noble EP, K Blum, T Ritchie, A Montgomery and PJ Sheridan (1991) Allelic association of the D2 dopamine receptor gene with receptor-binding characteristics in alcoholism.Arch. Gen. Psychiatry 48, 648–654.PubMedGoogle Scholar
  25. Noble EP, K Syndulko, J Fitch, T Ritchie, M Bohman, P Guth et al. (1994) D2 dopamine receptor Taq 1 alleles in medically ill alcoholic and nonalcoholic patients.Alcohol Alcohol. 29, 729–744.PubMedGoogle Scholar
  26. Noble EP, LA Gottschalk, JH Fallon, TL Ritchie and JC Wu (1997) D2 dopamine receptor polymorphism and brain regional glucose metabolism.Am. J. Med. Genet. 74, 162–166.PubMedCrossRefGoogle Scholar
  27. Pickens RW, DS Svikis, M McGue, DT Lykken, LL Heston and PJ Clayton (1991) Heterogeneity in the inheritance of alcoholism, a study of male and female twins.Arch. Gen. Psychiatry 48, 19–28.PubMedGoogle Scholar
  28. Pohjalainen T, JO Rinne, K Nagren, P Lehikoinen, K Anttila, EK Syvälahti and J Hietala (1998) The A1 allele of the human D2 dopamine receptor gene predicts low D2 receptor availability in healthy volunteers.Mol. Psychiatry 3, 256–260.PubMedCrossRefGoogle Scholar
  29. Ponce G, MA Jimenez-Arriero, G Rubio, J Hoenicka, I Ampuero, JA Ramos and T Palomo (2003) The A1 allele of the DRD2 gene (Ta q 1A polymorphism) is associated with antisocial personality in a sample of alcohol-dependent patients.Eur. Psychiatry 18, 356–360.PubMedCrossRefGoogle Scholar
  30. Schuckit MA (1981) Twin studies on substance abuse, an overview.Prog. Clin. Biol. Res. 69 Pt C, 61–70.PubMedGoogle Scholar
  31. Thompson J, N Thomas, A Singleton, M Piggott, S Lloyd, EK Perry, CM Morris, RH Perry, IN Ferrier and JA Court (1997) D2 dopamine receptor gene (DRD2) Ta q IA polymorphism, reduced dopamine D2 receptor binding in the human striatum associated with the A1 allele.Pharmacogenetics 7, 479–484.PubMedCrossRefGoogle Scholar
  32. Turner E, J Ewing, P Shilling, TL Smith, M Irwin, M Schuckit and JR Kelsoe (1992) Lack of association between an RFLP near the dopamine D2 receptor gene and severe alcoholism.Biol. Psychiatry 31, 285–290.PubMedCrossRefGoogle Scholar

Copyright information

© FP Graham Publishing Co 2004

Authors and Affiliations

  • G. Ponce
    • 1
  • J. Hoenicka
    • 1
  • R. Rodríguez-jiménez
    • 1
  • A. Gozalo
    • 2
  • M. Jimenéz
    • 1
  • R. Monasor
    • 1
  • M. Aragüés
    • 1
  • G. Rubio
    • 3
  • M. A. Jiménez-arriero
    • 1
  • J. A. Ramos
    • 4
  • T. Palomo
    • 1
  1. 1.Servicio de PsiquiatríaHospital Universitario 12 de OctubreMadridEspaña
  2. 2.Servicio de BioquímicaHospital Universitario 12 de OctubreMadridEspaña
  3. 3.Servicio de Salud Mental RetiroMadridEspaña
  4. 4.Departamento Bioquímica y Biología Molecular, Facultad de MedicinaUniversidad ComplutenseMadridEspaña

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