Hostname: page-component-8448b6f56d-c47g7 Total loading time: 0 Render date: 2024-04-23T20:08:04.776Z Has data issue: false hasContentIssue false
  • English
  • Français

Association analysis of the insertion/deletion polymorphism in serotonin transporter gene in patients with affective disorder

Published online by Cambridge University Press:  16 April 2020

Joanna Hauser ,
Anna Leszczyńska ,
Jerzy Samochowiec ,
Piotr M. Czerski ,
Agata Ostapowicz ,
Maria Chlopocka ,
Jan Horodnicki  and
Janusz K. Rybakowski
Joanna Hauser*
Affiliation:
Department of Adult Psychiatry, University of Medical Sciences, Poznan, Poland
Anna Leszczyńska
Affiliation:
Department of Adult Psychiatry, University of Medical Sciences, Poznan, Poland
Jerzy Samochowiec
Affiliation:
Department of Psychiatry, Pomeranian Academy of Medicine, Szczecin, Poland
Piotr M. Czerski
Affiliation:
Department of Adult Psychiatry, University of Medical Sciences, Poznan, Poland
Agata Ostapowicz
Affiliation:
Department of Psychiatry, Pomeranian Academy of Medicine, Szczecin, Poland
Maria Chlopocka
Affiliation:
Department of Adult Psychiatry, University of Medical Sciences, Poznan, Poland
Jan Horodnicki
Affiliation:
Department of Psychiatry, Pomeranian Academy of Medicine, Szczecin, Poland
Janusz K. Rybakowski
Affiliation:
Department of Adult Psychiatry, University of Medical Sciences, Poznan, Poland
*
*Email: j.hauser@wp.pl
Get access

Abstract

A polymorphism of serotonin transporter was studied in 226 patients with affective disorders (n = 132 for bipolar, n = 94 for unipolar affective disorder) and in 213 healthy subjects. Consensus diagnosis by at least two psychiatrists, according to the ICD-10 and DSM-IV criteria was made for each patient using SCID (Structured Clinical Interview for DSM-IV Axis I Disorders). A functional polymorphism in the promoter region of serotonin transporter gene, where 44 bp are either inserted (long allele) or deleted (short allele) was analysed. Genotype s/s was significantly more frequent in patients comparing to the control group (P = 0.011 for bipolar and P = 0.003 for unipolar affective disorder) - the most marked association was found in males with bipolar and unipolar illness. The allele frequencies also differ significantly between patients and controls (P = 0.003 for bipolar and P = 0.001 for unipolar affective disorder). The frequency of the low activity (short) allele was higher in patients than in controls (51.1% in bipolar, and 54.3 in unipolar vs 39.4% in controls). We suggest that the presence of allele s may increase the susceptibility to occurrence of affective disorder.

Keywords

PolymorphismSerotoninAffective disorders
Type
Short communication
Information
European Psychiatry , Volume 18 , Issue 3 , May 2003 , pp. 129 - 132
Copyright
Copyright © Éditions scientifiques et médicales Elsevier SAS 2003

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Barker, EL, Blakely, RD. Norepinephrine and serotonin transporters: molecular targets of antidepressant drugs. In: Bloom, FE, Kupfer, DJ, editors. Psychopharmacology; the fourth generation of progress. New York: Raven Press; 1995. p. 321–33.Google Scholar
Bellivier, F, Henry, C, Szoke, A, Schurhoff, F, Nosten-Bertrand, M, Feingold, J, et, al. Serotonin transporter gene polymorphisms in patients with unipolar or bipolar depression. Neurosci Lett 1998; 255(3):143–6.CrossRefGoogle ScholarPubMed
Bellivier, F, Szoke, A, Henry, C, Lacoste, J, Bottos, C, Nosten-Ber-trand, M, et al.Possible association between serotonin transporter gene polymorphism and violent suicidal behaviour mood disorders. Biol Psychiatry 2000;48(4):319–22.CrossRefGoogle ScholarPubMed
Bondy, B, Erfurth, A, de Jonge, S, Kruger, M, Meyer, H. Possible association of the short allele of the serotonin transporter promoter gene polymorphism (5-HTTLPR) with violent suicide. Mol Psychiatry 2000;5:193–5.CrossRefGoogle ScholarPubMed
Collier, DA, Stober, G, Li, T, Heils, A, Catalano, M, Di Bella, D, et al.A novel functional polymorphism within the promoter of the serotonin transporter gene: possible role in susceptibility to affective disorders. Mol Psychiatry 1996;1:453–60.Google ScholarPubMed
Frisch, A, Postilnick, D, Rockah, R, Michaelovsky, E, Postilnik, S, Birman, E, et al.Association of unipolar major depressive disorder with genes of the serotonergic and dopaminergic pathways. Mol Psychiatry 1999;4:389–92.CrossRefGoogle ScholarPubMed
Furlong, RA, Ho, L, Walsh, C, Rubinstein, JS, Jain, S, Paykel, ES, et al.Analysis and meta-analysis of two serotonin transporter gene polymorphism in bipolar and unipolar affective disorders. Am J Med Genet 1998;81(1):58–63.3.0.CO;2-V>CrossRefGoogle ScholarPubMed
Gelernter, J, Kranzler, H, Coccaro, EF, Siever, LJ, New, AS. Serotonin transporter protein gene polymorphism and personality measures in African, American and European American subjects. Am J Psychiatry 1998;155:1332–8.CrossRefGoogle ScholarPubMed
Greenberg, BD, Tolliver, TJ, Huang, SJ, Li, Q, Bengel, D, Murphy, DL. Genetic variation in the serotonin transporter promoter region affects serotonin uptake in human blood platelets. Am J Med Genet 1999; 88(1):83–7.3.0.CO;2-0>CrossRefGoogle ScholarPubMed
Gutierez, B, Arranz, MJ, Collier, DA, Valles, V, Gillamat, R, Bertran-petit, J, et al.Serotonin transporter gene and risk for bipolar affective disorder: an association study in Spanish population. Biol Psychiatry 1998;43(11):843–7.CrossRefGoogle Scholar
Hahn, MK, Blakley, RD. Monoamine transporter gene structure and polymorphisms in relation to psychiatric and other complex disorders. Pharmacogenomics J 2002;2:217–35.CrossRefGoogle ScholarPubMed
Hauser, J, Leszczyn´ska, A, Samochowiec, J, Ostapowicz, A, Czerski, P, Jaracz, J, et al.The association study of a functional polymorphism of the monoamine oxidase A gene promoter in patients with affective disorders. Arch Psychiatry Psychother 2002;4:9–15.Google Scholar
Heils, A, Mossner, R, Lesch, KP. The human serotonin transporter gene polymorphism-basic research and clinical implications. J Neural Transm 1997;104(10):1005–14.CrossRefGoogle ScholarPubMed
Heils, A, Teufel, A, Petri, S, Stober, G, Rieder, P, Bengel, D, et al.Allelic variation of human serotonin transporter gene expression. J Neuro-chem 1996;66:2621–4.Google ScholarPubMed
Hoehe, MR, Wendel, B, Grunewald, I, Chiaroni, P, Levy, N, Morris-Rosendahl, D, et al.Serotonin transporter (5-HTT) gene polymorphisms are not associated with susceptibility to mood disorders. Am J Med Genet 1998;81(1):1–3.3.0.CO;2-2>CrossRefGoogle Scholar
Kaiser, R, Muller-Oerlinghausen, B, Filler, D, Tremblay, PB, Berg-hofer, A, Roots, I, et al.Correlation between serotonin uptake in human blood platelets with the 44 bp polymorphism and the 17 bp variable number of tandem repeat of the serotonin transporter. Am J Med Genet 2002;114(3):323–8.CrossRefGoogle ScholarPubMed
Kim, DK, Lim, SW, Lee, S, Sohn, SE, Kim, S, Hahn, CG, et al.Serotonin transporter gene polymorphism and antidepressant response. Neuroreport 2000;11(1):215–9.CrossRefGoogle ScholarPubMed
Kunugi, H, Hattori, M, Kato, T, Tatsumi, M, Sakai, T, Sasaki, T, et al.Serotonin transporter gene polymorphisms: ethnic difference and possible association with bipolar affective disorder. Mol Psychiatry 1997;2(6):457–62.CrossRefGoogle ScholarPubMed
Lesch, KP, Mössner, R. Genetically driven variation in serotonin uptake: is there a link to affective spectrum, neurodevelopmental, and neurodegenerative disorders? Biol Psychiatry 1998;44:179–92.CrossRefGoogle Scholar
Lesch, KP, Wolozin, BL, Murphy, DL, Riederer, P. Primary structure of the human platelet serotonin uptake site: identity with the brain serotonin transporter. J Neurochem 1993;60:2319–21.Google ScholarPubMed
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;2:390–2.CrossRefGoogle ScholarPubMed
Mellerup, E, Bennike, B, Bolwig, T, Hasholt, L, Jorgensen, MB, Plenge, P, et al.Platelet serotonin transporters and the transporter gene in control subjects, unipolar patients and bipolar patients. Acta Psy-chiatryScand 2001;103:229–33.CrossRefGoogle ScholarPubMed
Miller, SA, Dykes, DD, Polesky, HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acid Res 1988; 16(3):1215.Google ScholarPubMed
Minov, C, Baghai, TC, Schule, C, Zwanzger, P, Schwarz, MJ, Zill, P, et al.Serotonin 2A-receptor and transporter polymorphisms: lack of association in patients with major depression. Neurosci Lett 2001;303(2): 119–22.CrossRefGoogle ScholarPubMed
Ohara, K, Nagai, M, Tsukamoto, T, Tani, K, Suzuki, Y, Ohara, K. Functional polymorphism in the serotonin transporter promoter at the SLC6A4 locus and mood disorders. Biol Psychiatry 1998;44(7): 550–4.CrossRefGoogle ScholarPubMed
Olivieira, JRM, Carvalho, DR, Pontual, D, Gallindo, RM, Sougey, EB, Gentil, V, et al.Analysis of the serotonin transporter polymorphism (5-HTTLPR) in Brazilian patients affected bydysthymia, major depression and bipolar disorder. Mol Psychiatry 2000;5(4):348–9.CrossRefGoogle Scholar
Ospina-Duque, J, Duque, C, Carvajal-Carmona, L, Ortiz-Barrientos, D, Soto, I, Pineda, N, et al.An association study of bipolar mood disorder (type I) with the 5-HTTLPR serotonin transporter polymorphism in a human population isolate from Colombia. Neurosci Lett 2000;292(3): 199–202.CrossRefGoogle Scholar
Povlock, SL, Amara, SG. The structure and function of norepinephrine, dopamine, and serotonin transporters. In: Reith, MEA, editor. Neurotransmitter transporters: structure, function, and regulation. Totowa, NJ: Humana Press; 1997. p. 1–28.Google Scholar
Ramamoorthy, S, Bauman, AL, Moore, KR, Han, H, Yang-Feng, T, Chang, AS, et al.Antidepressant- and cocaine-sensitive human serotonin transporter: molecular cloning, expression and chromosomal localization. Proc Natl Acad Sci USA 1993;90:2542–6.CrossRefGoogle ScholarPubMed
Rees, M, Norton, N, Jones, I, McCandless, F, Scourfield, J, Hol-mans, P, et al.Association studies of bipolar disorder at the human serotonin transporter gene (hSERT, 5HTT). Mol Psychiatry 1997; 2(5):398–402.CrossRefGoogle Scholar
Rosenthal, N, Mazzanti, C, Barnett, R, Hardin, TA, Turner, EH, Lam, GK, et al.Role of serotonin transporter promoter repeat length polymorphism (5-HTTLPR) in seasonalityand seasonal affective disorder. Mol Psychiatry 1998;3:175–7.CrossRefGoogle ScholarPubMed
Routledge, C, Middlemiss, DN. The 5-HT hypothesis of depression revisited. Mol Psychiatry 1996;1:437.Google ScholarPubMed
Serretti, A, Cusin, C, Lattuada, E, Di Bella, D, Catalano, M, Smeraldi, E. Serotonin transporter gene (5-HTTLPR) is not associated with depressive symptomatology in mood disorders. Mol Psychiatry 1999; 4:280–3.CrossRefGoogle Scholar
Steffens, DC, Svenson, I, Marchuk, DA, Levy, RM, Hays, JC, Flint, EP, et al.Allelic differences in the serotonin transporter-linked polymorphic region in geriatric depression. Am J Geriatr Psychiatry 2002;10(2):185–91.CrossRefGoogle ScholarPubMed
Vincent, JB, Masellis, M, Lawrence, J, Choi, V, Gurling, HM, et al.Genetic association analysis of serotonin system genes in bipolar affective disorder. Am J Psychiatry 1999;156:136–8.CrossRefGoogle ScholarPubMed
Submit a response

Comments

No Comments have been published for this article.