Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

The human serotonin transporter gene linked polymorphism (5-HTTLPR) shows ten novel allelic variants


The serotonin transporter (5-HTT) gene is a promising candidate for introducing the heritability of interindividual variation in personality and the genetic susceptibility for various psychiatric diseases. Transcription of the gene is modulated by a common polymorphism in its upstream regulatory region (5-HTT gene-linked polymorphic region: 5-HTTLPR). The 5-HTTLPR consists of variation of the repetitive sequence containing GC-rich, 20-23-bp-long repeat elements. A deletion/insertion in the 5-HTTLPR was first reported to create a short (S) allele and a long (L) allele (14- and 16-repeats, respectively). Three other kinds of alleles (18-, 19- and 20-repeats) in addition to the S and L alleles in 5-HTTLPR have been reported. In the present study, we examined the 5-HTTLPR polymorphism in detail and identified ten novel sequence variants, concluding that the alleles reported as S and L are divided into four and six kinds of allelic variant, respectively. Subsequently, we developed a method for genotyping. The total number of alleles (14-A, 14-B, 14-C, 14-D, 15, 16-A, 16-B, 16-C, 16-D, 16-E, 16-F, 19, 20 and 22) in the 5-HTTLPR was 14 in our populations (Japanese: n = 131; Caucasian: n = 74) in the present study. In addition, a significant ethnic difference between Japanese and Caucasian populations was observed for distributions of alleles and genotypes (P < 0.0001 and P < 0.0001, respectively). Our results suggest that the analyses of the 5-httlpr should be revised by genotyping with a more complete subdivision of alleles.

Your institute does not have access to this article

Relevant articles

Open Access articles citing this article.

Access options

Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Figure 1
Figure 2
Figure 3


  1. Ramamoorthy S, Bauman AL, Moore KR, Han H, Yang-Feng T, Cheng A et al. Antidepressant- and cocaine-sensitive human serotonin transporter: molecular cloning, expression, and chromosomal localization Proc Natl Acad Sci USA 1993; 90: 2542–2546

    CAS  Article  Google Scholar 

  2. Heils A, Teufel A, Petri S, Stober G, Riederer P, Bengel D et al. Allelic variation of human serotonin transporter gene expression J Neurochem 1996; 66: 1–4

    Google Scholar 

  3. Lesch KP, Bengel D, Heils A, Sabol SZ, Greenberg BD, Petri S et al. Association of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region Science 1996; 274: 1527–1531

    CAS  Article  Google Scholar 

  4. Collier DA, Stöber G, Li T, Heils A, Catalan M, Di Bella D et al. A promoter of the serotonin gene: possible role in susceptibility to affective disorder Mol Psychiatry 1996; 1: 453–460

    CAS  Google Scholar 

  5. Mortensen OV, Thomassen M, Larsen MB, Whittemore SR, Wiborg O . Functional analysis of a novel human serotonin transporter gene promoter in immortalized raphe cells Brain Res Mol Brain Res 1999; 68: 141–148

    CAS  Article  Google Scholar 

  6. Kunugi H, Hattori M, Kato T, Tatsumi M, Saki T, Sasaki T et al. Serotonin transporter gene polymorphisms: ethnic difference and possible association with bipolar affective disorder Mol Psychiatry 1997; 2: 457–462

    CAS  Article  Google Scholar 

  7. Malhotra AK, Goldman D, Mazzanti C, Clifton A, Breier A, Pickar D . A functional serotonin transporter (5-HTT) polymorphism is associated with psychosis in neuroleptic-free schizophrenics Mol Psychiatry 1998; 3: 328–332

    CAS  Article  Google Scholar 

  8. Mendes de Oliveira JR, Otto PA, Vallada H, Lauriano V, Elkis H, Lafer B et al. Analysis of a novel functional polymorphism within the promoter region of the serotonin transporter gene (5-HTT) in Brazilian patients affected by bipolar disorder and schizophrenia Am J Med Genet 1998; 81: 225–227

    CAS  Article  Google Scholar 

  9. Matsushita S, Muramatsu T, Kimura M, Shirakawa O, Mita T, Nakai T et al. Serotonin transporter gene regulatory region polymorphism and panic disorder Mol Psychiatry 1997; 2: 390–392

    CAS  Article  Google Scholar 

  10. Cook EH, Courchesne R, Lord C, Cox NJ, Yan S, Lincoln A et al. Evidence of linkage between the serotonin transporter and autistic disorder Mol Psychiatry 1997; 2: 247–250

    Article  Google Scholar 

  11. Klauck SM, Poustka F, Benner A, Lesch KP, Poustka A . Serotonin transporter (5-HTT) gene variants associated with autism? Hum Mol Genet 1997; 6: 2233–2238

    CAS  Article  Google Scholar 

  12. Flory JD, Manuck SB, Ferrell RE, Dent KM, Peters DG, Muldoon MF . Neuroticism is not associated with the serotonin transporter (5-HTTLPR) polymorphism Mol Psychiatry 1999; 4: 93–96

    CAS  Article  Google Scholar 

  13. Michaelovsky E, Frisch A, Rockah R, Peleg L, Magal N, Shohat M et al. A novel allele in the promoter region of the human serotonin transporter gene Mol Psychiatry 1999; 4: 97–99

    CAS  Article  Google Scholar 

  14. Delbrück SJ, Wendel B, Grunewald I, Sander T, Morris-Rosendahl D, Crocq MA et al. A novel allelic variant of the human serotonin transporter gene regulatory polymorphism Cytogenet Cell Genet 1997; 79: 214–220

    Article  Google Scholar 

  15. Stefan S, Jean-Marc K, David R, Laurent E . Arlequin: a Software for Population Genetic Data Analysis Genetics and Biometry Laboratory, University of Geneva: Switzerland 1997

    Google Scholar 

  16. Guo SW, Thompson EA . Performing the exact test of Hardy–Weinberg proportion for multiple alleles Biometrics 1992; 48: 361–372

    CAS  Article  Google Scholar 

  17. Raymond M, Rousset F . An exact test for population differentiation Evolution 1995; 49: 1280–1283

    Article  Google Scholar 

  18. Cooper DN, Krawczak M, Antonorakis SE . The Metabolic and Molecular Bases of Inherited Disease 7th edn. McGraw-Hill: New York 1995; pp259–291

    Google Scholar 

  19. Cooper DN, Krawczak M . Human Gene Mutation Bios Scientific: Oxford 1993

    Google Scholar 

  20. Bell GI, Selby MJ, Rutter WJ . The highly polymorphic region near the human insulin gene is composed of simple tandemly repeating sequences Nature 1982; 295: 286–292

    Google Scholar 

  21. Gelernter J, Cubells JF, Kidd JR, Pakstis AJ, Kidd KK . Population studies of polymorphisms of the serotonin transporter protein gene Am J Med Genet 1999; 88: 61–66

    CAS  Article  Google Scholar 

Download references


We would like to express our thanks to the subjects who participated in this study, to Miss Y Maruki for her technical assistance, and to Dr Y Nakamura of the University of Tokyo for providing genomic DNAs of the CEPH family members. This work was supported in part by a Grant-in-Aid for Co-operative Research from the Ministry of Education, Science, Sports and Culture of Japan.

Author information

Authors and Affiliations


Corresponding author

Correspondence to A Sano.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

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

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI:


  • serotonin transporter
  • functional polymorphism
  • novel alleles
  • ethnic difference

Further reading


Quick links