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An interaction between the serotonin transporter promoter region and dopamine transporter polymorphisms contributes to harm avoidance and reward dependence traits in normal healthy subjects

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Summary.

There is evidence for an association between polymorphisms of serotonin- and dopamine-related genes and temperamental personality traits. Recent findings have shown that interactions between allelic variants of the different genes may contribute to personality traits. We examined the effects of serotonin transporter-linked promoter region (5-HTTLPR) and dopamine transporter (DAT1) gene polymorphisms for associations with the Temperament and Character Inventory (TCI) temperament subscales in 209 Koreans. We found that the variants of 5-HTTLPR interacted with the DAT1 gene polymorphism to influence the HA and RD temperament subscales of TCI. Neither of these two genes affected any subscales of TCI alone.

Controlling for the effects of gender and age, we found significant interactions between 5-HTTLPR and DAT1 genes on Harm Avoidance (HA) and Reward Dependence (RD) as measured by the TCI (Hotelling’s Trace = 3.0, P = 0.02). In the presence of the DAT1 10/10 genotype, subjects of group L of 5-HTTLPR had a significantly higher HA score and significantly lower RD score than those of group S (F = 5.04, df = 1, p = 0.03 and F = 8.35, df = 1, p = 0.004, respectively).

These findings suggest that the variants of 5-HTTLPR interacted with the DAT1 gene polymorphism to influence the HA and RD temperament subscales of TCI.

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References

  • J Auerbach V Geller S Lezer E Shinwell RH Belmaker J Levine R Ebstein (1999) ArticleTitleDopamine D4 receptor (D4DR) and serotonin transporter promoter (5-HTTLPR) polymorphisms in the determination of temperament in 2-month-old infants Mol Psychiatry 4 IssueID4 369–373 Occurrence Handle10483054 Occurrence Handle1:CAS:528:DC%2BD3cXlvVWks78%3D Occurrence Handle10.1038/sj.mp.4000531

    Article  PubMed  CAS  Google Scholar 

  • F Bellivier C Henry A Szoke F Schurhoff M Nosten-Bertrand J Feingold JM Launay M Leboyer JL Laplanche (1998) ArticleTitleSerotonin transporter gene polymorphisms in patients with unipolar or bipolar depression Neurosci Lett 255 IssueID3 143–146 Occurrence Handle9832193 Occurrence Handle1:CAS:528:DyaK1cXmvFWmu74%3D Occurrence Handle10.1016/S0304-3940(98)00677-6

    Article  PubMed  CAS  Google Scholar 

  • TJJ Bouchard (1994) ArticleTitleGenes, environment, and personality Science 264 1700–1701 Occurrence Handle8209250

    PubMed  Google Scholar 

  • CR Cloninger (1986) ArticleTitleA unified biosocial theory of personality and its role in the development of anxiety states Psychiatr Dev 4 167–226 Occurrence Handle3809156 Occurrence Handle1:STN:280:DyaL2s7hvVajtw%3D%3D

    PubMed  CAS  Google Scholar 

  • CR Cloninger (1987) ArticleTitleA systematic method for clinical description and classification of personality variants Arch Gen Psychiatry 44 573–588 Occurrence Handle3579504 Occurrence Handle1:STN:280:DyaL2s3ht1eqtA%3D%3D

    PubMed  CAS  Google Scholar 

  • CR Cloninger DM Svrakic TR Przybeck (1993) ArticleTitleA psychobiological model of temperament and character Arch Gen Psychiatry 50 975–990 Occurrence Handle8250684 Occurrence Handle1:STN:280:DyaK2c%2FntFGqsQ%3D%3D

    PubMed  CAS  Google Scholar 

  • DA Collier G Stober T Li A Heils M Catalano D Di Bella MJ Arranz RM Murray HP Vallada D Bengel CR Muller GW Roberts E Smeraldi G Kirov P Sham KP Lesch (1996) ArticleTitleA novel functional polymorphism within the promoter of the serotonin transporter gene: possible role in susceptibility to affective disorders Mol Psychiatry 1 IssueID6 453–460 Occurrence Handle9154246 Occurrence Handle1:CAS:528:DyaK2sXnsVGqtw%3D%3D

    PubMed  CAS  Google Scholar 

  • EH Cook SuffixJr MA Stein MD Krasowski NJ Cox DM Olkon JE Kieffer BL Leventhal (1995) ArticleTitleAssociation of attention-deficit disorder and the dopamine transporter gene Am J Hum Genet 56 IssueID4 993–998 Occurrence Handle7717410 Occurrence Handle1:CAS:528:DyaK2MXlt1eltrk%3D

    PubMed  CAS  Google Scholar 

  • RP Ebstein R Segman J Benjamin Y Osher L Nemanov RH Belmaker (1997) ArticleTitle5-HT2C (HTR2C) serotonin receptor gene polymorphism associated with the human personality trait of reward dependence: interaction with dopamine D4 receptor (D4DR) and dopamine D3 receptor (D3DR) polymorphisms Am J Med Genet 74 IssueID1 65–72 Occurrence Handle9034010 Occurrence Handle1:STN:280:DyaK2s7os1Cgtw%3D%3D Occurrence Handle10.1002/(SICI)1096-8628(19970221)74:1<65::AID-AJMG15>3.0.CO;2-P

    Article  PubMed  CAS  Google Scholar 

  • S Fuke S Suo N Takahashi H Koike N Sasagawa S Ishiura (2001) ArticleTitleThe VNTR polymorphism of the human dopamine transporter (DAT1) gene affects gene expression Pharmacogenomics J 1 IssueID2 152–156 Occurrence Handle11911442 Occurrence Handle1:CAS:528:DC%2BD3MXnt1elu7g%3D

    PubMed  CAS  Google Scholar 

  • M Gill G Daly S Heron Z Hawi M Fitzgerald (1997) ArticleTitleConfirmation of association between attention deficit hyperactivity disorder and a dopamine transporter polymorphism Mol Psychiatry 2 311–313 Occurrence Handle9246671 Occurrence Handle1:STN:280:DyaK2szovFCruw%3D%3D Occurrence Handle10.1038/sj.mp.4000290

    Article  PubMed  CAS  Google Scholar 

  • B Giros MG Caron (1993) ArticleTitleMolecular characterization of the dopamine transporter Trends Pharmacol Sci 14 43–49 Occurrence Handle8480373 Occurrence Handle1:CAS:528:DyaK3sXisVOks7w%3D Occurrence Handle10.1016/0165-6147(93)90029-J

    Article  PubMed  CAS  Google Scholar 

  • HJ Grabe M Lange B Wolff H Volzke M Lucht HJ Freyberger U John I Cascorbi (2005) ArticleTitleMental and physical distress is modulated by a polymorphism in the 5-HT transporter gene interacting with social stressors and chronic disease burden Mol Psychiatry 10 IssueID2 220–224 Occurrence Handle15263905 Occurrence Handle1:CAS:528:DC%2BD2MXnt1Slsg%3D%3D Occurrence Handle10.1038/sj.mp.4001555

    Article  PubMed  CAS  Google Scholar 

  • BD Greenberg Q Li FR Lucas S Hu LA Sirota J Benjamin KP Lesch D Hamer DL Murphy (2000) ArticleTitleAssociation between the serotonin transporter promoter polymorphism and personality traits in a primarily female population sample Am J Med Genet 96 IssueID2 202–216 Occurrence Handle10893498 Occurrence Handle1:STN:280:DC%2BD3cvitlymsg%3D%3D Occurrence Handle10.1002/(SICI)1096-8628(20000403)96:2<202::AID-AJMG16>3.0.CO;2-J

    Article  PubMed  CAS  Google Scholar 

  • B Ham Y Kim M Choi J Cha Y Choi MS Lee (2004) ArticleTitleSerotonergic genes and personality traits in the Korean population Neurosci Lett 354 2–5 Occurrence Handle14698468 Occurrence Handle1:CAS:528:DC%2BD3sXpvF2lu74%3D Occurrence Handle10.1016/S0304-3940(03)00753-5

    Article  PubMed  CAS  Google Scholar 

  • HM Han TH Yeom YW Shin KH Kim DJ Yoon KJ Cheong (1986) ArticleTitleStandization study of Korean version Beck Depression Inventory Korean J Neuropsychiatry 25 487–500

    Google Scholar 

  • AC Heath CR Cloninger NG Martin (1994) ArticleTitleTesting a model for the genetic structure of personality: a comparison of the personality systems of Cloninger and Eysenck J Pers Soc Psychol 66 IssueID4 762–775 Occurrence Handle8189351 Occurrence Handle1:STN:280:DyaK2c3ks1Ggug%3D%3D Occurrence Handle10.1037/0022-3514.66.4.762

    Article  PubMed  CAS  Google Scholar 

  • A Heils A Teufel S Petri G Stober P Riederer D Bengel KP Lesch (1996) ArticleTitleAllelic variation of human serotonin transporter gene expression J Neurochem 66 2621–2624 Occurrence Handle8632190 Occurrence Handle1:CAS:528:DyaK28XjtFCrsrk%3D Occurrence Handle10.1046/j.1471-4159.1996.66062621.x

    Article  PubMed  CAS  Google Scholar 

  • AF Jorm AS Henderson PA Jacomb H Christensen AE Korten B Rodgers X Tan S Easteal (2000) ArticleTitleAssociation of smoking and personality with a polymorphism of the dopamine transporter gene: results from a community survey Am J Med Genet 96 IssueID3 331–334 Occurrence Handle10898910 Occurrence Handle1:STN:280:DC%2BD3czptVWqsA%3D%3D Occurrence Handle10.1002/1096-8628(20000612)96:3<331::AID-AJMG19>3.0.CO;2-0

    Article  PubMed  CAS  Google Scholar 

  • AF Jorm M Prior A Sanson D Smart Y Zhang S Easteal (2001) ArticleTitleAssociation of a polymorphism of the dopamine transporter gene with externalizing behavior problems and associated temperament traits: a longitudinal study from infancy to the mid-teens Am J Med Genet 105 IssueID4 346–350 Occurrence Handle11378848 Occurrence Handle1:STN:280:DC%2BD3M3pslSisA%3D%3D Occurrence Handle10.1002/ajmg.1355

    Article  PubMed  CAS  Google Scholar 

  • S Kapur G Remington (1996) ArticleTitleSerotonin-dopamine interaction and its relevance to schizophrenia Am J Psychiatry 153 IssueID4 466–476 Occurrence Handle8599393 Occurrence Handle1:STN:280:DyaK287nvFWmtA%3D%3D

    PubMed  CAS  Google Scholar 

  • S Katsuragi H Kunugi A Sano T Tsutsumi K Isogawa S Nanko J Akiyoshi (1999) ArticleTitleAssociation between serotonin transporter gene polymorphism and anxiety-related traits Biol Psychiatry 45 IssueID3 368–370 Occurrence Handle10023516 Occurrence Handle1:STN:280:DyaK1M7kslGqtQ%3D%3D Occurrence Handle10.1016/S0006-3223(98)00090-0

    Article  PubMed  CAS  Google Scholar 

  • DK Kim MY Seo S Lim H Kim S Kim (2003) ArticleTitleSerotonin transporter gene polymorphisms and its phenotypic characteristics expressed in platelet [3H]-serotonin uptake study in Korean depressed patients J Korean Neuropsychiatr Assoc 42 IssueID1 54–60 Occurrence Handle1:CAS:528:DC%2BD3sXhsVOlurk%3D

    CAS  Google Scholar 

  • SJ Kim YS Kim NK Choi HJ Hong HS Lee CH Kim (2005a) ArticleTitleSerotonin transporter gene polymorphism and personality traits in a korean population Neuropsychobiology 51 IssueID4 243–247 Occurrence Handle10.1159/000085819 Occurrence Handle1:CAS:528:DC%2BD2MXkvVOnsbY%3D

    Article  CAS  Google Scholar 

  • YS Kim BL Leventhal SJ Kim BN Kim KA Cheon HJ Yoo J Badner EH Cook (2005b) ArticleTitleFamily-based association study of DAT1 and DRD4 polymorphism in Korean children with ADHD Neurosci Lett 390 IssueID3 176–181 Occurrence Handle1:CAS:528:DC%2BD2MXhtFersrrK Occurrence Handle10.1016/j.neulet.2005.08.025

    Article  CAS  Google Scholar 

  • KU Kuhn K Meyer MM Nothen M Gansicke A Papassotiropoulos W Maier (1999) ArticleTitleAllelic variants of dopamine receptor D4 (DRD4) and serotonin receptor 5HT2c (HTR2c) and temperament factors: replication tests Am J Med Genet 88 IssueID2 168–172 Occurrence Handle10206238 Occurrence Handle1:STN:280:DyaK1M3itFSkuw%3D%3D Occurrence Handle10.1002/(SICI)1096-8628(19990416)88:2<168::AID-AJMG14>3.0.CO;2-P

    Article  PubMed  CAS  Google Scholar 

  • ES Lander RJ Schorck (1994) ArticleTitleGenetic dissection of complex traits Science 365 2037–2048

    Google Scholar 

  • HJ Lee HS Lee YK Kim L Kim MS Lee IK Jung KY Suh S Kim (2003a) ArticleTitleD2 and D4 dopamine receptor gene polymorphisms and personality traits in a young Korean population Am J Med Genet 121B IssueID1 44–49 Occurrence Handle10.1002/ajmg.b.20054

    Article  Google Scholar 

  • HJ Lee HS Lee YK Kim SH Kim L Kim MS Lee SH Joe IK Jung KY Suh S Kim (2003b) ArticleTitleAllelic variants interaction of dopamine receptor D4 polymorphism correlate with personality traits in young Korean female population Am J Med Genet 118B IssueID1 76–80 Occurrence Handle10.1002/ajmg.b.10047

    Article  Google Scholar 

  • KP Lesch D Bengel A Heils SZ Sabol BD Greenberg S Petri J Benjamin D Hamer DL Murphy (1996) ArticleTitleAssociation of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region Science 274 1527–1531 Occurrence Handle8929413 Occurrence Handle1:CAS:528:DyaK28Xnt1ansL8%3D Occurrence Handle10.1126/science.274.5292.1527

    Article  PubMed  CAS  Google Scholar 

  • J Melke L Westberg S Nilsson M Landen H Soderstrom F Baghaei R Rosmond G Holm P Bjorntorp LG Nilsson R Adolfsson E Eriksson (2003) ArticleTitleA polymorphism in the serotonin receptor 3A (HTR3A) gene and its association with harm avoidance in women Arch Gen Psychiatry 60 IssueID10 1017–1023 Occurrence Handle14557147 Occurrence Handle1:CAS:528:DC%2BD3sXos12nuro%3D Occurrence Handle10.1001/archpsyc.60.10.1017

    Article  PubMed  CAS  Google Scholar 

  • J Mill P Asherson C Browes U D’Souza I Craig (2002) ArticleTitleExpression of the dopamine transporter gene is regulated by the 3′ UTR VNTR: evidence from brain and lymphocytes using quantitative RT-PCR Am J Med Genet 114 IssueID8 975–979 Occurrence Handle12457396 Occurrence Handle10.1002/ajmg.b.10948

    Article  PubMed  Google Scholar 

  • RJ Mitchell S Howlett L Earl NG White J McComb MS Schanfield I Briceno SS Papiha L Osipova G Livshits WR Leonard MH Crawford (2000) ArticleTitleDistribution of the 3′ VNTR polymorphism in the human dopamine transporter gene in world populations Hum Biol 72 IssueID2 295–304 Occurrence Handle10803661 Occurrence Handle1:STN:280:DC%2BD3c3mtVyjtA%3D%3D

    PubMed  CAS  Google Scholar 

  • F Murakami T Shimomura K Kotani S Ikawa E Nanba K Adachi (1999) ArticleTitleAnxiety traits associated with a polymorphism in the serotonin transporter gene regulatory region in the Japanese J Hum Genet 44 15–17 Occurrence Handle9929970 Occurrence Handle1:CAS:528:DyaK1MXms1Gmug%3D%3D Occurrence Handle10.1007/s100380050098

    Article  PubMed  CAS  Google Scholar 

  • DL Murphy GR Uhl A Holmes R Ren-Patterson FS Hall I Sora S Detera-Wadleigh KP Lesch (2003) ArticleTitleExperimental gene interaction studies with SERT mutant mice as models for human polygenic and epistatic traits and disorders Genes Brain Behav 2 IssueID6 350–364 Occurrence Handle14653307 Occurrence Handle1:CAS:528:DC%2BD2cXptFOl Occurrence Handle10.1046/j.1601-1848.2003.00049.x

    Article  PubMed  CAS  Google Scholar 

  • Y Osher D Hamer J Benjamin (2000) ArticleTitleAssociation and linkage of anxiety-related traits with a functional polymorphism of the serotonin transporter gene regulatory region in Israeli sibling pairs Mol Psychiatry 5 IssueID2 216–219 Occurrence Handle10822353 Occurrence Handle1:CAS:528:DC%2BD3cXlslart7Y%3D Occurrence Handle10.1038/sj.mp.4000660

    Article  PubMed  CAS  Google Scholar 

  • S Prisco S Pagannone E Esposito (1994) ArticleTitleSerotonin-dopamine interaction in the rat ventral tegmental area: an electrophysiological study in vivo J Pharmacol Exp Ther 271 IssueID1 83–90 Occurrence Handle7965760 Occurrence Handle1:CAS:528:DyaK2MXitVKns7c%3D

    PubMed  CAS  Google Scholar 

  • SZ Sabol ML Nelson C Fisher L Gunzerath CL Brody S Hu LA Sirota SE Marcus BD Greenberg FRt Lucas J Benjamin DL Murphy DH Hamer (1999) ArticleTitleA genetic association for cigarette smoking behavior Health Psychol 18 IssueID1 7–13 Occurrence Handle9925040 Occurrence Handle1:STN:280:DyaK1M7it1Chug%3D%3D Occurrence Handle10.1037/0278-6133.18.1.7

    Article  PubMed  CAS  Google Scholar 

  • J Samochowiec J Kucharska-Mazur F Rybakowski A Ostapowicz J Horodnicki M Rozpara R Kaminski A Skrzypinska G Arentowicz H Rommelspacher LG Schmidt (2002) ArticleTitleNorepinephrine transporter polymorphism and personality trait of reward dependence in male alcoholics Pharmacopsychiatry 35 IssueID5 195–196 Occurrence Handle12237791 Occurrence Handle1:CAS:528:DC%2BD38Xot1WhtLY%3D Occurrence Handle10.1055/s-2002-34117

    Article  PubMed  CAS  Google Scholar 

  • J Samochowiec F Rybakowski P Czerski M Zakrzewska G Stepien J Pelka-Wysiecka J Horodnicki JK Rybakowski J Hauser (2001) ArticleTitlePolymorphisms in the dopamine serotonin, and norepinephrine transporter genes and their relationship to temperamental dimensions measured by the Temperament and Character Inventory in healthy volunteers Neuropsychobiology 43 IssueID4 248–253 Occurrence Handle11340364 Occurrence Handle1:CAS:528:DC%2BD3MXktlCju78%3D Occurrence Handle10.1159/000054898

    Article  PubMed  CAS  Google Scholar 

  • J Samochowiec S Syrek P Michal A Ryzewska-Wodecka A Samochowiec J Horodnicki M Zakrzewska J Kucharska-Mazur (2004) ArticleTitlePolymorphisms in the serotonin transporter and monoamine oxidase A genes and their relationship to personality traits measured by the Temperament and Character Inventory and NEO Five-Factor Inventory in healthy volunteers Neuropsychobiology 50 IssueID2 174–181 Occurrence Handle15292674 Occurrence Handle1:CAS:528:DC%2BD2cXmsV2itLw%3D Occurrence Handle10.1159/000079111

    Article  PubMed  CAS  Google Scholar 

  • A Sano K Kondoh Y Kakimoto I Kondo (1993) ArticleTitleA 40-nucleotide repeat polymorphism in the human dopamine transporter gene Hum Genet 91 405–406 Occurrence Handle8500798 Occurrence Handle1:CAS:528:DyaK3sXlvFKqs7w%3D Occurrence Handle10.1007/BF00217369

    Article  PubMed  CAS  Google Scholar 

  • M Shinohara H Mizushima M Hirano K Shioe M Nakazawa Y Hiejima Y Ono S Kanba (2004) ArticleTitleEating disorders with binge-eating behaviour are associated with the s allele of the 3′-UTR VNTR polymorphism of the dopamine transporter gene J Psychiatry Neurosci 29 IssueID2 134–137 Occurrence Handle15069467

    PubMed  Google Scholar 

  • I Sora FS Hall AM Andrews M Itokawa XF Li HB Wei C Wichems KP Lesch DL Murphy GR Uhl (2001) ArticleTitleMolecular mechanisms of cocaine reward: combined dopamine and serotonin transporter knockouts eliminate cocaine place preference Proc Natl Acad Sci USA 98 IssueID9 5300–5305 Occurrence Handle11320258 Occurrence Handle1:CAS:528:DC%2BD3MXjt1Ontr0%3D Occurrence Handle10.1073/pnas.091039298

    Article  PubMed  CAS  Google Scholar 

  • J Stevens (1996) Applied multivariate statistics for the social science EditionNumber3 Lawrence Erlbaum Associates Mahwah, New Jersey

    Google Scholar 

  • SM Sung JH Kim E Yang YK Abrams IK Lyoo (2002) ArticleTitleReliability and validity of the Korean version of the temperament and character inventory Compr Psychiatry 43 IssueID3 235–243 Occurrence Handle11994844 Occurrence Handle10.1053/comp.2002.30794

    Article  PubMed  Google Scholar 

  • A Szekely Z Ronai Z Nemoda G Kolmann J Gervai M Sasvari-Szekely (2004) ArticleTitleHuman personality dimensions of persistence and harm avoidance associated with DRD4 and 5-HTTLPR polymorphisms Am J Med Genet 126B IssueID1 106–110 Occurrence Handle10.1002/ajmg.b.20134 Occurrence Handle1:STN:280:DC%2BD2c7ltlGlsQ%3D%3D Occurrence Handle15048658

    Article  CAS  PubMed  Google Scholar 

  • A Thapar J Holmes K Poulton R Harrington (1999) ArticleTitleGenetic basis of attention deficit and hyperactivity Br J Psychiatry 174 105–111 Occurrence Handle10211163 Occurrence Handle1:STN:280:DyaK1M3islKjuw%3D%3D Occurrence Handle10.1192/bjp.174.2.105

    Article  PubMed  CAS  Google Scholar 

  • T Umekage M Tochigi T Marui C Kato H Hibino T Otani K Kohda N Kato T Sasaki (2003) ArticleTitleSerotonin transporter-linked promoter region polymorphism and personality traits in a Japanese population Neurosci Lett 337 IssueID1 13–16 Occurrence Handle12524160 Occurrence Handle1:CAS:528:DC%2BD3sXmvVGn Occurrence Handle10.1016/S0304-3940(02)01291-0

    Article  PubMed  CAS  Google Scholar 

  • ID Waldman DC Rowe A Abramowitz ST Kozel JH Mohr SL Sherman HH Cleveland ML Sanders JM Gard C Stever (1998) ArticleTitleAssociation and linkage of the dopamine transporter gene and attention-deficit hyperactivity disorder in children: heterogeneity owing to diagnostic subtype and severity Am J Hum Genet 63 IssueID6 1767–1776 Occurrence Handle9837830 Occurrence Handle1:CAS:528:DyaK1MXlt1Sjug%3D%3D Occurrence Handle10.1086/302132

    Article  PubMed  CAS  Google Scholar 

  • SP Yook JS Kim (1997) ArticleTitleClinical study of Korean version Beck Anxiety Inventory: comparisons between patients and non-patients groups Korean J Clin Psychol 16 IssueID1 185–197

    Google Scholar 

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Kim, S., Kim, Y., Lee, H. et al. An interaction between the serotonin transporter promoter region and dopamine transporter polymorphisms contributes to harm avoidance and reward dependence traits in normal healthy subjects. J Neural Transm 113, 877–886 (2006). https://doi.org/10.1007/s00702-006-0444-3

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