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Association Study on Pathological Gambling and Polymorphisms of Dopamine D1, D2, D3, and D4 Receptor Genes in a Korean Population

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Abstract

Several studies have reported that some dopaminergic receptor polymorphisms are associated with pathological gambling (PG). Considering that there are major race and ethnic group difference in dopaminergic polymorphisms, the result of genetic association studies should be confirmed in more homogeneous population to avoid problems of population stratification. The present study aimed to investigate whether selected polymorphisms in the dopamine receptors genes (DRD1, DRD2, DRD3, and DRD4) are associated with PG in Korean population which is consisted of only Korean ancestry. Subjects were 104 men with a diagnosis of PG and 114 unrelated age-matched normal control men. Genotyping was performed for the DRD1 gene –48 A/G, DRD2 gene TaqI A, DRD3 gene Ser9Gly, and DRD4 gene exon III variable number tandem repeat polymorphisms. The method of multifactor dimensionality reduction (MDR) was used to analyze gene–gene interactions. There were no differences in the frequencies of any studied polymorphisms between patients with PG and normal controls. MDR analysis did not show a significant effect of the 4 dopamine receptor gene polymorphisms on susceptibility to PG (P > 0.05). The present study suggests that the analyzed polymorphisms of the dopamine receptor genes might not be associated with PG in a Korean population.

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References

  • American Psychiatric Association. (1980). Diagnostic and statistical manual of mental disorders. Washington, DC: American Psychiatric Association.

    Google Scholar 

  • Bergh, C., Eklund, T., Sodersten, P., & Nordin, C. (1997). Altered dopamine function in pathological gambling. Psychological Medicine, 27, 473–475.

    Article  PubMed  CAS  Google Scholar 

  • Berlin, I., de Brettes, B., Aymard, G., Diquet, B., Arnulf, I., & Puech, A. J. (2000). Dopaminergic drug response and the genotype (Taq IA polymorphism) of the dopamine D2 receptor. The International Journal of Neuropsychopharmacology, 3, 35–43.

    Article  PubMed  CAS  Google Scholar 

  • Blanco, C., Petkova, E., Ibanez, A., & Saiz-Ruiz, J. (2002). A pilot placebo-controlled study of fluvoxamine for pathological gambling. Annals of Clinical Psychiatry, 14, 9–15.

    PubMed  Google Scholar 

  • Blaszczynski, A., & Nower, L. (2002). A pathways model of problem and pathological gambling. Addiction, 97, 487–499.

    Article  PubMed  Google Scholar 

  • Blaszczynski, A. P., Wilson, A. C., & McConaghy, N. (1986). Sensation seeking and pathological gambling. British Journal of Addiction, 81, 113–117.

    Article  PubMed  CAS  Google Scholar 

  • Choi, W. C., Kim, K. B., Oh, D. W., & Lee, T. K. (2001). A preliminary study on standardization of Korean form of South Oak Gambling Screening. Journal of Korean Academy of Addiction Psychiatry, 5, 46–52.

    Google Scholar 

  • Cichon, S., Nothen, M. M., Stober, G., Schroers, R., Albus, M., Maier, W., et al. (1996). Systematic screening for mutations in the 5’-regulatory region of the human dopamine D1 receptor (DRD1) gene in patients with schizophrenia and bipolar affective disorder. American Journal of Medical Genetics, 67, 424–428.

    Article  PubMed  CAS  Google Scholar 

  • Comings, D. E., Ferry, L., Bradshaw-Robinson, S., Burchette, R., Chiu, C., & Muhleman, D. (1996a). The dopamine D2 receptor (DRD2) gene: A genetic risk factor in smoking. Pharmacogenetics, 6, 73–79.

    Article  PubMed  CAS  Google Scholar 

  • Comings, D. E., Muhleman, D., & Gysin, R. (1996b). Dopamine D2 receptor (DRD2) gene and susceptibility to posttraumatic stress disorder: A study and replication. Biological Psychiatry, 40, 368–372.

    Article  PubMed  CAS  Google Scholar 

  • Comings, D. E., Gade, R., Wu, S., Chiu, C., Dietz, G., Muhleman, D., et al. (1997). Studies of the potential role of the dopamine D1 receptor gene in addictive behaviors. Molecular Psychiatry, 2, 44–56.

    Article  PubMed  CAS  Google Scholar 

  • Comings, D. E., Gonzalez, N., Wu, S., Gade, R., Muhleman, D., Saucier, G., et al. (1999). Studies of the 48 bp repeat polymorphism of the DRD4 gene in impulsive, compulsive, addictive behaviors: Tourette syndrome, ADHD, pathological gambling, and substance abuse. American Journal of Medical Genetics, 88, 358–368.

    Article  PubMed  CAS  Google Scholar 

  • Crocq, M. A., Mant, R., Asherson, P., Williams, J., Hode, Y., Mayerova, A., et al. (1992). Association between schizophrenia and homozygosity at the dopamine D3 receptor gene. Journal of Medical Genetics, 29, 858–860.

    Article  PubMed  CAS  Google Scholar 

  • Cunningham-Williams, R. M., & Cottler, L. B. (2001). The epidemiology of pathological gambling. Seminars in Clinical Neuropsychiatry, 6, 155–166.

    Article  PubMed  CAS  Google Scholar 

  • da Silva Lobo, D. S., Vallada, H. P., Knight, J., Martins, S. S., Tavares, H., Gentil, V., et al. (2007). Dopamine genes and pathological gambling in discordant sib-pairs. Journal of Gambling Studies, 23, 421–433.

    Article  PubMed  Google Scholar 

  • Drevets, W. C., Videen, T. O., Price, J. L., Preskorn, S. H., Carmichael, S. T., & Raichle, M. E. (1992). A functional anatomical study of unipolar depression. Journal of Neuroscience, 12, 3628–3641.

    PubMed  CAS  Google Scholar 

  • Ebstein, R. P., Novick, O., Umansky, R., Priel, B., Osher, Y., Blaine, D., et al. (1996). Dopamine D4 receptor (D4DR) exon III polymorphism associated with the human personality trait of Novelty Seeking. Nature Genetics, 12, 78–80.

    Article  PubMed  CAS  Google Scholar 

  • Gallagher, D. A., O’Sullivan, S. S., Evans, A. H., Lees, A. J., & Schrag, A. (2007). Pathological gambling in Parkinson’s disease: Risk factors and differences from dopamine dysregulation. An analysis of published case series. Movement Disorders, 22, 1757–1763.

    Article  PubMed  Google Scholar 

  • Grandy, D. K., Zhang, Y., & Civelli, O. (1993). PCR detection of the TaqA RFLP at the DRD2 locus. Human Molecular Genetics, 2, 2197.

    Article  PubMed  CAS  Google Scholar 

  • Hwang, N.-Y., Yun, K.-W., Joo, Y. H., Kim, C. Y., Jung, S. H., Kim, B., et al. (2004). Association between schizophrenia and the genetic polymorphism of DRD3, DRD4 and HTR2A. Korean Journal of Laboratory Medicine, 24, 446–451.

    Google Scholar 

  • Jellinger, K. A. (1991). Pathology of Parkinson’s disease. Changes other than the nigrostriatal pathway. Molecular and Chemical Neuropathology, 14, 153–197.

    Article  PubMed  CAS  Google Scholar 

  • Kim, J. W., Park, C. S., Hwang, J. W., Shin, M. S., Hong, K. E., Cho, S. C., et al. (2006). Clinical and genetic characteristics of Korean male alcoholics with and without attention deficit hyperactivity disorder. Alcohol and Alcoholism, 41, 407–411.

    Article  PubMed  CAS  Google Scholar 

  • Kotler, M., Cohen, H., Segman, R., Gritsenko, I., Nemanov, L., Lerer, B., et al. (1997). Excess dopamine D4 receptor (D4DR) exon III seven repeat allele in opioid-dependent subjects. Molecular Psychiatry, 2, 251–254.

    Article  PubMed  CAS  Google Scholar 

  • Lang, A. E., & Obeso, J. A. (2004). Challenges in Parkinson’s disease: Restoration of the nigrostriatal dopamine system is not enough. Lancet Neurology, 3, 309–316.

    Article  PubMed  Google Scholar 

  • Lee, M. S., & Ryu, S. H. (2002). No association between the dopamine D3 receptor gene and Korean alcohol dependence. Psychiatric Genetics, 12, 173–176.

    Article  PubMed  Google Scholar 

  • Lee, S. H., Ham, B. J., Cho, Y. H., Lee, S. M., & Shim, S. H. (2007). Association study of dopamine receptor D2 TaqI A polymorphism and reward-related personality traits in healthy Korean young females. Neuropsychobiology, 56, 146–151.

    Article  PubMed  CAS  Google Scholar 

  • Linnet, J., Peterson, E., Doudet, D. J., Gjedde, A., & Moller, A. (2010). Dopamine release in ventral striatum of pathological gamblers losing money. Acta Psychiatrica Scandinavica, 122, 326–333.

    Article  PubMed  Google Scholar 

  • Liu, H.-C., Chen, C.-K., Leu, S.-J., Wu, H.-T., & Lin, S.-K. (2006). Association between dopamine receptor D1 A-48G polymorphism and methamphetamine abuse. Psychiatry and Clinical Neurosciences, 60, 226–231.

    Article  PubMed  CAS  Google Scholar 

  • Miller, R. D., Phillips, M. S., Jo, I., Donaldson, M. A., Studebaker, J. F., Addleman, N., et al. (2005). High-density single-nucleotide polymorphism maps of the human genome. Genomics, 86, 117–126.

    Article  PubMed  CAS  Google Scholar 

  • Moore, J. H. (2004). Computational analysis of gene–gene interactions using multifactor dimensionality reduction. Expert Review of Molecular Diagnostics, 4, 795–803.

    Article  PubMed  CAS  Google Scholar 

  • Motsinger, A. A., & Ritchie, M. D. (2006). Multifactor dimensionality reduction: An analysis strategy for modelling and detecting gene–gene interactions in human genetics and pharmacogenomics studies. Human Genomics, 2, 318–328.

    PubMed  CAS  Google Scholar 

  • Nanko, S., Hattori, M., Ikeda, K., Sasaki, T., Kazamatsuri, H., & Kuwata, S. (1993). Dopamine D4 receptor polymorphism and schizophrenia. Lancet, 341, 689–690.

    Article  PubMed  CAS  Google Scholar 

  • Nestler, E. J. (2004). Molecular mechanisms of drug addiction. Neuropharmacology, 47(Suppl 1), 24–32.

    Article  PubMed  CAS  Google Scholar 

  • Noble, E. P., Blum, K., Khalsa, M. E., Ritchie, T., Montgomery, A., Wood, R. C., et al. (1993). Allelic association of the D2 dopamine receptor gene with cocaine dependence. Drug and Alcohol Dependence, 33, 271–285.

    Article  PubMed  CAS  Google Scholar 

  • Noble, E. P., St Jeor, S. T., Ritchie, T., Syndulko, K., St Jeor, S. C., Fitch, R. J., et al. (1994). D2 dopamine receptor gene and cigarette smoking: A reward gene? Medical Hypotheses, 42, 257–260.

    Article  PubMed  CAS  Google Scholar 

  • Ono, Y., Manki, H., Yoshimura, K., Muramatsu, T., Mizushima, H., Higuchi, S., et al. (1997). Association between dopamine D4 receptor (D4DR) exon III polymorphism and novelty seeking in Japanese subjects. American Journal of Medical Genetics, 74, 501–503.

    Article  PubMed  CAS  Google Scholar 

  • O’Sullivan, S. S., & Lees, A. J. (2007). Pathological gambling in Parkinson’s disease. Lancet Neurology, 6, 384–386.

    Article  PubMed  Google Scholar 

  • Perez de Castro, I., Ibanez, A., Torres, P., Saiz-Ruiz, J., & Fernandez-Piqueras, J. (1997). Genetic association study between pathological gambling and a functional DNA polymorphism at the D4 receptor gene. Pharmacogenetics, 7, 345–348.

    PubMed  CAS  Google Scholar 

  • Procopio, M. (2005). Pathological gambling and cross-addiction. Canadian Journal of Psychiatry, 50, 302–303. author reply 303.

    Google Scholar 

  • Quickfall, J., & Suchowersky, O. (2007). Pathological gambling associated with dopamine agonist use in restless legs syndrome. Parkinsonism and Related Disorders, 13, 535–536.

    Article  PubMed  Google Scholar 

  • Ritchie, M. D., Hahn, L. W., & Moore, J. H. (2003). Power of multifactor dimensionality reduction for detecting gene–gene interactions in the presence of genotyping error, missing data, phenocopy, and genetic heterogeneity. Genetic Epidemiology, 24, 150–157.

    Article  PubMed  Google Scholar 

  • Shi, J., Gershon, E. S., & Liu, C. (2008). Genetic associations with schizophrenia: Meta-analyses of 12 candidate genes. Schizophrenia Research, 104, 96–107.

    Article  PubMed  Google Scholar 

  • Smith, D., Harvey, P., Battersby, M., Pols, R., Oakes, J., & Baigent, M. (2010). Treatment outcomes and predictors of drop out for problem gamblers in South Australia: A cohort study. Australian and New Zealand Journal of Psychiatry, 44, 911–920.

    Article  PubMed  Google Scholar 

  • Sokoloff, P., Giros, B., Martres, M. P., Bouthenet, M. L., & Schwartz, J. C. (1990). Molecular cloning and characterization of a novel dopamine receptor (D3) as a target for neuroleptics. Nature, 347, 146–151.

    Article  PubMed  CAS  Google Scholar 

  • Wang, T. Y., Lee, S. Y., Chen, S. L., Chen, S. H., Chu, C. H., Huang, S. Y., et al. (2011). The aldehyde dehydrogenase 2 gene is associated with heroin dependence. Drug Alcohol Depend. doi:10.1016/j.drugalcdep.2011.06.008.

  • Wiesbeck, G. A., Dursteler-MacFarland, K. M., Wurst, F. M., Walter, M., Petitjean, S., Muller, S., et al. (2006). No association of dopamine receptor sensitivity in vivo with genetic predisposition for alcoholism and DRD2/DRD3 gene polymorphisms in alcohol dependence. Addiction Biology, 11, 72–75.

    Article  PubMed  CAS  Google Scholar 

  • Woo, S. I., Kim, J. W., Rha, E., Han, S. H., Hahn, K. H., Park, C. S., et al. (2002). Association of the Ser9Gly polymorphism in the dopamine D3 receptor gene with tardive dyskinesia in Korean schizophrenics. Psychiatry and Clinical Neurosciences, 56, 469–474.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Psychiatry, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, 108, Pyung-dong, Seoul, Jongno-Ku, 110-746, Republic of Korea

    Sewon Lim, Juwon Ha & Young-Chul Shin

  2. Department of Addiction Rehabilitation and Social Welfare, Eulji University, Seongnam-si, Gyeonggi-do, Republic of Korea

    Sam-Wook Choi

  3. Department of Psychiatry, Catholic University of Daegu School of Medicine, 3056-6, Daemyeong 4-dong, Daegu, Nam-gu, South Korea

    Seung-Gul Kang

Authors
  1. Sewon Lim
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  2. Juwon Ha
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  3. Sam-Wook Choi
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  4. Seung-Gul Kang
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  5. Young-Chul Shin
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Correspondence to Young-Chul Shin.

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Sewon Lim and Juwon Ha contributed equally to this work.

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Lim, S., Ha, J., Choi, SW. et al. Association Study on Pathological Gambling and Polymorphisms of Dopamine D1, D2, D3, and D4 Receptor Genes in a Korean Population. J Gambl Stud 28, 481–491 (2012). https://doi.org/10.1007/s10899-011-9261-1

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  • DOI: https://doi.org/10.1007/s10899-011-9261-1

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