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Association between Novelty Seeking and the −521 C/T polymorphism in the promoter region of the DRD4 gene

Molecular Psychiatry volume 6, pages 35–38 (2001)Cite this article

Abstract

Association between the human personality trait ‘Novelty Seeking’ and the polymorphism of the DRD4 gene was first reported by Ebstein1 and Benjamin2 in 1996. This was soon followed by replication studies in various ethnic groups and by studying the role of other neurotransmitter receptor and transporter genes in the genetic determination of human temperament. More recently, several polymorphic sites of the upstream regulatory region of the DRD4 gene have been described.3 Among these the −521 C/T single nucleotide polymorphism (SNP) was shown to be associated with the Novelty Seeking (NS) scores of the Temperament and Character Inventory (TCI) in a Japanese male population.4 We have investigated the −521 C/T SNP polymorphism in a Caucasian (Hungarian) population,5 and here we report a replication of the Japanese findings, in an association study involving 109 healthy Hungarian volunteers. We found a weak association between NS and CC vs CT or TT genotypes (P < 0.06). examination of this relation in male and female sex groups, however, strengthened the association for females (P < 0.01), but showed no genotypic effect for males.

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References

  1. Ebstein RP, Novick O, Umansky R, Priel B, Osher Z, 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

    Article  CAS  PubMed  Google Scholar 

  2. 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

    Article  CAS  PubMed  Google Scholar 

  3. Mitsuyasu H, Ozawa H, Takeda Y, Fukumaki Y . Novel polymorphisms in the upstream region of the human dopamine D4 receptor (DRD4) gene J Hum Genet 1999 44: 416–418

    Article  CAS  PubMed  Google Scholar 

  4. Okuyama Y, Ishiguru H, Nankai M, Shibuya H, Watabane 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

    Article  CAS  PubMed  Google Scholar 

  5. Ronai Z, Barta C, Guttman A, Lakatos K, Gervai J, Staub M et al. Genotyping the −521 C/T functional polymorphism in the promoter region of the dopamine D4 receptor (DRD4) gene by agarose gel electrophoresis Electrophoresis (in press)

  6. Heath AC, Cloninger CR, Martin NG . Testing a model for genetic structure of personality: a comparison of the personality system of Cloninger and Eysenck J Pers Soc Psychol 1994 66: 782–775

    Article  Google Scholar 

  7. Bergeman CS, Bergeman CS, Chipuer HM, Plomin R, Pedersen NL, Mcclearn GE et al. Genetic and environmental effect on openness to experience, agreeableness, and conscientiousness: an adoption/twin study J Pers 1993 61: 159–179

    Article  CAS  PubMed  Google Scholar 

  8. Plomin R, Owen MJ, McGuffin P . The genetic bases of complex behaviors Science 1994 264: 1733–1739

    Article  CAS  PubMed  Google Scholar 

  9. Cloninger CR, Svarick DM, Prybeck TR . A psychobiological model of temperament and character Arch Gen Psychiatry 1993 50: 975–990

    Article  CAS  PubMed  Google Scholar 

  10. Ebstein RP, Belmaker RH . Saga of an adventure gene: Novelty Seeking, substance abuse and the dopamine D4 receptor (DRD4) exon III repeat polymorphism Mol Psychiatry 1995 2: 381–384

    Article  Google Scholar 

  11. 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

    Article  CAS  PubMed  Google Scholar 

  12. Paterson AD, Glen A, Kennedy JL . Dopamine D4 receptor gene: Novelty or nonsense Neuropsychopharmacology 1999 21: 3–16

    Article  CAS  PubMed  Google Scholar 

  13. Comings DE, Gonzales N, Wu S, Gade R, Muhleman D, Saucier G et al. Polymorphism of the DRD4 gene in impulsive, compulsive, addictive behaviours: Tourette syndrome, ADHD, pathological gambling and substance abuse Am J Med Gen (Psychiatric Gen) 1999 88: 358–368

    Article  CAS  Google Scholar 

  14. Kamakura S, Iwaki A, Matsumoto M, Fukumaki Y . Cloning and characterization of the 5′-flanking region of the human dopamine D4 receptor gene Biochem Biophys Res Commun 1997 235: 321–326

    Article  CAS  PubMed  Google Scholar 

  15. Okuyama Y, Ishiguro H, Toru M, Arinami T . A genetic polymorphism in the promoter region of DRD4 associated with expression of schizophrenia Biochem Biophys Res Commun 1999 258: 292–295

    Article  CAS  PubMed  Google Scholar 

  16. Chang FM, Kidd JR, Livak KJ, Pakstis AJ, Kidd KK . The world-wide distribution of allele frequencies at the human dopamine D4 receptor locus Hum Genet 1996 98: 91–101

    Article  CAS  PubMed  Google Scholar 

  17. Nakamura M, Ueno S, Sano A, Tanabe H . The human serotonin transporter gene linked polymorphism (5-HTTLPR) shows ten novel allelic variants Mol Psychiatry 2000 5: 32–38

    Article  CAS  PubMed  Google Scholar 

  18. Van Tol HHM . Structural and functional characteristics of the dopamine D4 receptor Adv Pharmacol 1998 42: 486–490

    Article  CAS  PubMed  Google Scholar 

  19. Van Tol HHM, Wu CM, Guan HC, Ohara K, Bunzow JR, Civelli O et al. Multiple dopamine D4 receptor variants in the human population Nature 1992 358: 149–152

    Article  CAS  PubMed  Google Scholar 

  20. Catalano M, Nobile M, Novelli E, Nothen MM, Smeraldi E . Distribution of a novel mutation in the first exon of the human dopamine D4 receptor gene in psychotic patients Biol Psychiatry 1993 34: 459–464

    Article  CAS  PubMed  Google Scholar 

  21. Cichon S, Nothen MM, Catalano M, Di Bella D, Maier W, Lichtermann D et al. Identification of two novel polymorphisms and a rare deletion variant in the human dopamine receptor gene Am J Med Gen (Psychiatric Gen) 1995 5: 97–103

    CAS  Google Scholar 

  22. Seeman P, Ulpian C, Chouinard G, Van Tol HH, Dwosh H, Lieberman JA et al. Dopamine D4 receptor variant, D4-GLYCINE194, in Africans, but not in Caucasians: no association with schizophrenia Am J Med Genet 1994 54: 384–390

    Article  CAS  PubMed  Google Scholar 

  23. Wilson JM, Sanyal S, Van Tol HHM . Dopamine D2 and D4 receptor ligands: relation to antipsychotic action Eur J Pharmacol 1998 351: 273–286

    Article  CAS  PubMed  Google Scholar 

  24. Benjamin J, Osher Y, Kotler M, Gritsenko I, Nemanov L, Belmaker RH et al. Association between tridimensional personality questionnaire (TPQ) traits and three functional polymorphisms: dopamine receptor D4 (DRD4), serotonin transporter promoter region (5-HTTLPR) and cathecol O-methyltransferase (COMT) Mol Psychiatry 2000 5: 96–100

    Article  CAS  PubMed  Google Scholar 

  25. Ebstein RP, Nemanov L, Klotz I, Grietsenko I, Belmaker RH . Additional evidence for an association between the dopamine D4 receptor (DRD4) exon polymorphism and the human personality trait of Novelty Seeking Mol Psychiatry 1997 2: 472–477

    Article  CAS  PubMed  Google Scholar 

  26. Meulenbelt I, Droog S, Trommelen GJ, Boomsma DI, Slagboom PE . High-yield noninvasive human genomic DNA isolation method for genetic studies in geographically dispersed families and populations Am J Hum Genet 1995 57: 1252–1255

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Lichter JB, Barr CL, Kennedy JL, Van Tol HH, Kidd KK, Livak KJ . A hypervariable segment in the human dopamine receptor D4 (DRD4) gene Hum Mol Genet 1993 2: 767–773

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We would like to express our appreciation to J Nagy and S Rozsa (Department of Personality and Clinical Psychology, Institute of Psychology, Lorand Eotvos University, Budapest) for providing the Hungarian version of TCI and for valuable discussions. This work was supported by the Hungarian National grants ETT 30/2000, OTKA F 030075 and FKFP 0658/1999.

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  1. Z Ronai and A Szekely: Co-first authors based on equal contributions in separate (psychological and genetic) components of the study

Authors and Affiliations

  1. Institute of Medical Chemistry, Molecular Biology and Pathobiochemistry, Semmelweis University, Budapest POB 260, 1444, Hungary

    Z Ronai, Z Nemoda, M Staub & M Sasvari-Szekely

  2. Institute of Psychology, Lorand Eotvos University, Budapest POB 4, 1378, Hungary

    A Szekely

  3. Social Development Group, Institute of Psychology, Hungarian Academy of Sciences, Budapest POB 398, 1394, Hungary

    K Lakatos & J Gervai

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  1. Z Ronai
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Correspondence to M Sasvari-Szekely.

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Ronai, Z., Szekely, A., Nemoda, Z. et al. Association between Novelty Seeking and the −521 C/T polymorphism in the promoter region of the DRD4 gene. Mol Psychiatry 6, 35–38 (2001). https://doi.org/10.1038/sj.mp.4000832

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