Korean Journal of Biological Psychiatry (생물정신의학)

The Korean Society of Biological Psychiatry (대한생물정신의학회)
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The Association among the Genetic Polymorphism of Dopamine D4 Receptor, Temperament and Alcohol Drinking Behavior in Young Korean Adults

초기 성인기 한국인에서 도파민 D4 수용체의 유전적 다형성, 기질특성, 음주행동 사이의 연관성

  • Nam, Yeong-Woo (Department of Psychiatry, School of Medicine, Chungbuk National University College of Medicine) ;
  • Lee, Sang-Ick (Department of Psychiatry, School of Medicine, Chungbuk National University College of Medicine) ;
  • Shin, Chul-Jin (Department of Psychiatry, School of Medicine, Chungbuk National University College of Medicine) ;
  • Son, Jung-Woo (Department of Psychiatry, School of Medicine, Chungbuk National University College of Medicine) ;
  • Kim, Sie-Kyeong (Department of Psychiatry, School of Medicine, Chungbuk National University College of Medicine)
  • 남영우 (충북대학교 의과대학 신경정신과학교실) ;
  • 이상익 (충북대학교 의과대학 신경정신과학교실) ;
  • 신철진 (충북대학교 의과대학 신경정신과학교실) ;
  • 손정우 (충북대학교 의과대학 신경정신과학교실) ;
  • 김시경 (충북대학교 의과대학 신경정신과학교실)
  • Received : 2011.01.03
  • Accepted : 2011.04.05
  • Published : 2011.05.31
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Abstract

Objectives The aim of this study is to explore the association among DRD4 polymorphism, temperament and alcohol drinking behavior of Koreans in their early adulthood. Method Participants were 172 healthy Korean adults (mean age $28.1{\pm}0.8$). Their temperament was assessed with the Temperament and Character Inventory (TCI) and their alcohol drinking behavior were evaluated with a self-reported questionnaire including the CAGE and the Korean version of Alcohol Use Disorder Identification Test (AUDIT-K). DRD4 exon III 48 base pair variable number of tandem repeats (VNTR) was genotyped by PCR. Results No significant association was found between DRD4 polymorphism and TCI temperament dimension (novelty seeking, harm avoidance, reward dependence, and persistence) as well as alcohol drinking behavior scales. However, novelty seeking was significantly associated with alcohol drinking behavior. The higher level of novelty seeking was associated with the higher severity index of drinking (B = -0.225, p < 0.001) and problematic alcohol use on the CAGE and AUDIT-K [Odds Ratio (OR) = 1.111, 95% Confidence Interval (CI) 1.021-1.209, p = 0.015, OR = 1.087, 95% CI 1.009-1.170, p = 0.028]. Conclusion In our study, while there is no significant association of DRD4 polymorphism with temperament and alcohol drinking behavior, novelty seeking affects problematic alcohol use. Results suggest that novelty seeking may play an important role in problematic alcohol use in young Korean adults.

Keywords

References

  1. Tyndale RF. Genetics of alcohol and tobacco use in humans. Ann Med 2003;35:94-121. https://doi.org/10.1080/07853890310010014
  2. Noble EP, Ozkaragoz TZ, Ritchie TL, Zhang X, Belin TR, Sparkes RS. D2 and D4 dopamine receptor polymorphisms and personality. Am J Med Genet 1998;81:257-267. https://doi.org/10.1002/(SICI)1096-8628(19980508)81:3<257::AID-AJMG10>3.0.CO;2-E
  3. Cox WM, Klinger E. A motivational model of alcohol use. J Abnorm Psychol 1988;97:168-180. https://doi.org/10.1037/0021-843X.97.2.168
  4. Lee JI, Lee JS, Cho SN, Chai YG, Nam JH, Yang BH, et al. Acute alcohol responses and personality traits by aldehyde dehydrogenase 2 genotype variances in patients with alcohol dependence. Korean J Biol Psychiatry 2005;12:196-206.
  5. Cooper ML, Frone MR, Russell M, Mudar P. Drinking to regulate positive and negative emotions: a motivational model of alcohol use. J Pers Soc Psychol 1995;69:990-1005. https://doi.org/10.1037/0022-3514.69.5.990
  6. Chung YC, Eun HB, Li B, Zhang WX. A cross-cultural study of drinking behaviors and perceptions in Korean and Chinese students. J Korean Neuropsychiatr Assoc 1999;38:317-324.
  7. Cloninger CR. Neurogenetic adaptive mechanisms in alcoholism. Science 1987;236:410-416. https://doi.org/10.1126/science.2882604
  8. Vallone D, Picetti R, Borrelli E. Structure and function of dopamine receptors. Neurosci Biobehav Rev 2000;24:125-132. https://doi.org/10.1016/S0149-7634(99)00063-9
  9. Grady DL, Chi HC, Ding YC, Smith M, Wang E, Schuck S, et al. High prevalence of rare dopamine receptor D4 alleles in children diagnosed with attention-deficit hyperactivity disorder. Mol Psychiatry 2003;8:536-545. https://doi.org/10.1038/sj.mp.4001350
  10. Ono Y, Manki H, Yoshimura K, Muramatsu T, Mizushima H, Higuchi S, et al. Association between dopamine D4 receptor (D4DR) exon III polymorphism and novelty seeking in Japanese subjects. Am J Med Genet 1997;74:501-503. https://doi.org/10.1002/(SICI)1096-8628(19970919)74:5<501::AID-AJMG9>3.0.CO;2-Q
  11. Tomitaka M, Tomitaka S, Otuka Y, Kim K, Matuki H, Sakamoto K, et al. Association between novelty seeking and dopamine receptor D4 (DRD4) exon III polymorphism in Japanese subjects. Am J Med Genet 1999;88:469-471. https://doi.org/10.1002/(SICI)1096-8628(19991015)88:5<469::AID-AJMG6>3.0.CO;2-F
  12. Benjamin J, Li L, Patterson C, Greenberg BD, Murphy DL, Hamer DH. Population and familial association between the D4 dopamine receptor gene and measures of Novelty Seeking. Nat Genet 1996; 12:81-84. https://doi.org/10.1038/ng0196-81
  13. Ebstein RP, Novick O, Umansky R, Priel B, Osher Y, Blaine D, et al. Dopamine D4 receptor (D4DR) exon III polymorphism associated with the human personality trait of Novelty Seeking. Nat Genet 1996;12:78-80. https://doi.org/10.1038/ng0196-78
  14. Laucht M, Becker K, El-Faddagh M, Hohm E, Schmidt MH. Association of the DRD4 exon III polymorphism with smoking in fifteen- year-olds: a mediating role for novelty seeking? J Am Acad Child Adolesc Psychiatry 2005;44:477-484. https://doi.org/10.1097/01.chi.0000155980.01792.7f
  15. Kluger AN, Siegfried Z, Ebstein RP. A meta-analysis of the association between DRD4 polymorphism and novelty seeking. Mol Psychiatry 2002;7:712-717. https://doi.org/10.1038/sj.mp.4001082
  16. Ryu SH, Lee MS. Allelic Association of the Dopamine D4 Receptor Gene in Korean Alcoholism. Korean J Biol Psychiatr 2001;8:246- 250.
  17. Kim MY, Park JM, Yoon GI, Rue TG, Gwon DH, Kim SG, et al. Novelty seeking in substance use disorder. J Kor Soc Biological Therpies in psychiatry 2001;7:112-119.
  18. Kim BL, Lee SI, Kim H, Shin CJ, Sohn JW, Chi KH, et al. Effects of psychosocial factors and the genotypes of aldehyde dehydrogenase II and tryptophan hydroxylase on the alcohol use in freshmen of a university. Korean J Psychopharmacol 2004;15:361-370.
  19. Lee HJ, Lee HS, Kang HY, Kim L, Lee MS, Suh KY, et al. Association between dopamine receptor D4 polymorphisms and novelty seeking personality trait in a Korean population. J Korean Neuropsychiatr Assoc 2002;41:630-637.
  20. Mitsuyasu H, Hirata N, Sakai Y, Shibata H, Takeda Y, Ninomiya H, et al. Association analysis of polymorphisms in the upstream region of the human dopamine D4 receptor gene (DRD4) with schizophrenia and personality traits. J Hum Genet 2001;46:26-31. https://doi.org/10.1007/s100380170120
  21. Cloninger CR, Przybeck T, Svrakic D. Temperament and Character Inventory (TCI) : a guide to its development and use. Washington Univ, St Luis, Missouri, Center for psychobiology of personality; 1994.
  22. Sung SM, Kim JH, Yang E, Abrams KY, Lyoo IK. Reliability and validity of the Korean version of the Temperament and Character Inventory. Compr Psychiatry 2002;43:235-243. https://doi.org/10.1053/comp.2002.30794
  23. Kim SK. Genetic Polymorphisms of Alcohol Metabolizing Enzymes and Psychosocial Factors Affecting the Change of Alcohol Drinking Behaviors in Korean Young Adults [dissertation]. Cheongju: Chungbuk National University; 2009.
  24. Ewing JA. Screening for alcoholism using CAGE. Cut down, Annoyed, Guilty, Eye opener. JAMA 1998;280:1904-1905. https://doi.org/10.1001/jama.280.22.1904
  25. Lee BO, Lee CH, Lee PG, Choi MJ, Namkoong K. Development of Korean Version of Alcohol Use Disorders Identification Test (AUDIT- K): Its Reliability and Validity, J Korean Academy of Addiction Psychiatry 2000;4:83-92.
  26. MunafO MR, Yalcin B, Willis-Owen SA, Flint J. Association of the dopamine D4 receptor (DRD4) gene and approach-related personality traits: meta-analysis and new data. Biol Psychiatry 2008;63:197- 206. https://doi.org/10.1016/j.biopsych.2007.04.006
  27. Verweij KJ, Zietsch BP, Medland SE, Gordon SD, Benyamin B, Nyholt DR, et al. A genome-wide association study of Cloninger's temperament scales: implications for the evolutionary genetics of personality. Biol Psychol 2010;85:306-317. https://doi.org/10.1016/j.biopsycho.2010.07.018
  28. Szekely A, Ronai Z, Nemoda Z, Kolmann G, Gervai J, Sasvari-Szekely M. Human personality dimensions of persistence and harm avoidance associated with DRD4 and 5-HTTLPR polymorphisms. Am J Med Genet B Neuropsychiatr Genet 2004;126B:106-110. https://doi.org/10.1002/ajmg.b.20134
  29. Kim SJ, Kim YS, Kim CH, Lee HS. Lack of association between polymorphisms of the dopamine receptor D4 and dopamine transporter genes and personality traits in a Korean population. Yonsei Med J 2006;47:787-792. https://doi.org/10.3349/ymj.2006.47.6.787
  30. Tsai SJ, Hong CJ, Yu YW, Chen TJ. Association study of catechol-Omethyltransferase gene and dopamine D4 receptor gene polymorphisms and personality traits in healthy young chinese females. Neuropsychobiology 2004;50:153-156. https://doi.org/10.1159/000079107
  31. Tochigi M, Hibino H, Otowa T, Kato C, Marui T, Ohtani T, et al. Association between dopamine D4 receptor (DRD4) exon III polymorphism and Neuroticism in the Japanese population. Neurosci Lett 2006;398:333-336. https://doi.org/10.1016/j.neulet.2006.01.020
  32. Lusher J, Ebersole L, Ball D. Dopamine D4 receptor gene and severity of dependence. Addict Biol 2000;5:469-472. https://doi.org/10.1111/j.1369-1600.2000.tb00217.x
  33. Cloninger CR, Przybeck TR, Svrakic DM. The Tridimensional Personality Questionnaire: U.S. normative data. Psychol Rep 1991;69: 1047-1057. https://doi.org/10.2466/pr0.1991.69.3.1047
  34. Durston S, Fossella JA, Casey BJ, Hulshoff Pol HE, Galvan A, Schnack HG, et al. Differential effects of DRD4 and DAT1 genotype on fronto-striatal gray matter volumes in a sample of subjects with attention deficit hyperactivity disorder, their unaffected siblings, and controls. Mol Psychiatry 2005;10:678-685. https://doi.org/10.1038/sj.mp.4001649
  35. Okuyama Y, Ishiguro H, Nankai M, Shibuya H, Watanabe A, Arinami T. Identification of a polymorphism in the promoter region of DRD4 associated with the human novelty seeking personality trait. Mol Psychiatry 2000;5:64-69. https://doi.org/10.1038/sj.mp.4000563
  36. Ray LA, Bryan A, Mackillop J, McGeary J, Hesterberg K, Hutchison KE. The dopamine D Receptor (DRD4) gene exon III polymorphism, problematic alcohol use and novelty seeking: direct and mediated genetic effects. Addict Biol 2009;14:238-244. https://doi.org/10.1111/j.1369-1600.2008.00120.x
  37. Vaughn MG, Beaver KM, DeLisi M, Howard MO, Perron BE. Dopamine D4 receptor gene exon III polymorphism associated with binge drinking attitudinal phenotype. Alcohol 2009;43:179-184. https://doi.org/10.1016/j.alcohol.2009.02.001
  38. Ishiguro H, Saito T, Shibuya H, Arinami T. Association study between genetic polymorphisms in the 14-3-3 eta chain and dopamine D4 receptor genes and alcoholism. Alcohol Clin Exp Res 2000;24: 343-347.
  39. Howard MO, Kivlahan D, Walker RD. Cloninger's tridimensional theory of personality and psychopathology: applications to substance use disorders. J Stud Alcohol 1997;58:48-66. https://doi.org/10.15288/jsa.1997.58.48
  40. Basiaux P, le Bon O, Dramaix M, Massat I, Souery D, Mendlewicz J, et al. Temperament and Character Inventory (TCI) personality profile and sub-typing in alcoholic patients: a controlled study. Alcohol Alcohol 2001;36:584-587. https://doi.org/10.1093/alcalc/36.6.584
  41. Cloninger CR, Svrakic DM, Przybeck TR. A psychobiological model of temperament and character. Arch Gen Psychiatry 1993;50:975- 990. https://doi.org/10.1001/archpsyc.1993.01820240059008