Serotonin transporter promoter and intron 2 polymorphisms: relationship between allelic variants and gene expression
Abstract
Background Two polymorphic regions of serotonin transporter (5-HTT) gene: a 44 base pair (bp) insertion/deletion in the promoter region (5-HTTLPR) and a 17 bp variable number of tandem repeats in second intron (VNTR-2), seem to modulate the gene's transcription in allele-dependent manner.Methods We have earlier demonstrated association with 5-HTT gene in families multiply affected by schizophrenia. Here, we investigated separate and combined effects of VNTR-2 and 5-HTTLPR on the rate of peripheral 5-HTT transcription in a sample of offspring from those families. Relative 5-HTT mRNA levels were determined in 53 permanent lymphoblast cell lines by semiquantitative real-time polymerase chain reaction using beta-actin as reference.Results Since the low-expressing alleles (short [S], 10) appeared to act dominantly, genotypes were grouped as "high-expressing" (long [L]/L, 12/12) versus "low-expressing" (S, 10). At both loci, nonsignificant differences in 5-HTT mRNA levels ( approximately 30%) were observed between "high"- and "low-expressing" genotypes. In order to search for the potential combined effect of 5-HTTLPR and VNTR-2, levels of 5-HTT mRNA were compared among three groups of samples having "low-expressing" genotype at none, one, or both loci. Increase in number of "low-expressing" genotypes significantly reduced relative 5-HTT gene expression (p <.02).Conclusions Our results indicate weak individual influence, but possible combined effect, of 5-HTTLPR and VNTR-2 polymorphisms on 5-HTT gene expression.
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The 12-repeat allele of STin2 is associated with reduced transcription compared with the 10-repeat allele.
“compared with the 10-repeat allele, the 12-repeat allele is also associated with reduced transcription (35).”
From Social disadvantage, genetic sensitivity, and children's telomere length (2014) · cites this paper as [35]
Cites
Lesch, K.-P., Bengel, D., Heils, A., Sabol, S. Z., Greenberg, B. D., Petri, S., Benjamin, J., Müller, C. R., Hamer, D. H., & Murphy, D. L. (1996) · Science · doi:10.1126/science.274.5292.1527 · Cited by 5,162 · see citing works
Bustin, S. A. (2000) · Journal of Molecular Endocrinology · doi:10.1677/jme.0.0250169 · Cited by 3,844 · see citing works
Serotonin transporter genetic variation and the response of the human amygdala.
Hariri, A. R., Mattay, V. S., Tessitore, A., Kolachana, B., Fera, F., Goldman, D., Egan, M. F., & Weinberger, D. R. (2002) · Science · doi:10.1126/science.1071829 · Cited by 2,340 · see citing works
Allelic Variation of Human Serotonin Transporter Gene Expression
Heils, A., Teufel, A., Petri, S., Stöber, G., Riederer, P., Bengel, D., & Lesch, K. P. (1996) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1996.66062621.x · Cited by 2,221 · see citing works
McGuffin, P. (1991) · Archives of General Psychiatry · doi:10.1001/archpsyc.1991.01810320088015 · Cited by 1,483 · see citing works
Ramamoorthy, S., Bauman, A. L., Moore, K. R., Han, H. J., Yang‐Feng, T. L., Chang, A. S., Ganapathy, V., & Blakely, R. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.6.2542 · Cited by 880 · see citing works
Organization of the human serotonin transporter gene
Lesch, K., Balling, U., Groß, J., Strauss, K. M., Wolozin, B. L., Murphy, D. L., & Riederer, P. F. (1994) · Journal of Neural Transmission · doi:10.1007/bf01276434 · Cited by 628 · see citing works
Heinz, A., Jones, D. W., Mazzanti, C. M., Goldman, D. A., Ragan, P. W., Hommer, D. W., Linnoila, M., & Weinberger, D. R. (2000) · Biological Psychiatry · doi:10.1016/s0006-3223(99)00171-7 · Cited by 462 · see citing works
Little, K. Y., McLaughlin, D. P., Zhang, L., Livermore, C. S., Dalack, G. W., McFinton, P. R., DelProposto, Z., Hill, E. M., Cassin, B. J., Watson, S. J., et al. (1998) · American Journal of Psychiatry · doi:10.1176/ajp.155.2.207 · Cited by 382 · see citing works
MacKenzie, A., & Quinn, J. P. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.26.15251 · Cited by 374 · see citing works
Serotonin Uptake Sites and Serotonin Receptors Are Altered in the Limbic System of Schizophrenics
Joyce, J. N., Shane, A. L., Lexow, N., Winokur, A., Casanova, M. F., & Kleinman, J. E. (1993) · Neuropsychopharmacology · doi:10.1038/npp.1993.32 · Cited by 340 · see citing works
Lesch, K., & Mößner, R. (1998) · Biological Psychiatry · doi:10.1016/s0006-3223(98)00121-8 · Cited by 334 · see citing works
Population studies of polymorphisms of the serotonin transporter protein gene.
Gelernter, J. E., Cubells, J. F., Kidd, J. R., PAKSTIS, A. J., & Kídd, K. K. (1999) · PubMed · Cited by 256 · see citing works
FISKERSTRAND, C. E., Lovejoy, E. A., & Quinn, J. P. (1999) · FEBS Letters · doi:10.1016/s0014-5793(99)01150-3 · Cited by 253 · see citing works
The Role of RNA Editing in Controlling Glutamate Receptor Channel Properties
SEEBURG, P. H. (1996) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1996.66010001.x · Cited by 233 · see citing works
Mößner, R., Daniel, S., Albert, D., Heils, A., Okladnova, O., Schmitt, A. G., & Lesch, K. (2000) · Neurochemistry International · doi:10.1016/s0197-0186(99)00122-9 · Cited by 172 · see citing works
Shioe, K., Ichimiya, T., Suhara, T., Takano, A., Sudo, Y., Yasuno, F., Hirano, M., Shinohara, M., Kagami, M., Okubo, Y., et al. (2003) · Synapse · doi:10.1002/syn.10204 · Cited by 168 · see citing works
Hanna, G. L. (1998) · Neuropsychopharmacology · doi:10.1016/s0893-133x(97)00097-3 · Cited by 150 · see citing works
Stoltenberg, S. F., Twitchell, G. R., Hanna, G. L., Cook, E. H., Fitzgerald, H. E., Zucker, R. A., & Little, K. Y. (2002) · American Journal of Medical Genetics · doi:10.1002/ajmg.10187 · Cited by 143 · see citing works
Malhotra, A. K., Goldman, D. A., Mazzanti, C. M., Clifton, A. D., Breier, A. F., & Pickar, D. (1998) · Molecular Psychiatry · doi:10.1038/sj.mp.4000412 · Cited by 132 · see citing works
Lovejoy, E. A., Scott, A. C., Fiskerstrand, C. E., et al. (2003) · European Journal of Neuroscience · doi:10.1046/j.1460-9568.2003.02446.x · Cited by 124 · see citing works
Willeit, M., Stastny, J., Pirker, W., Praschak-Rieder, N., Neumeister, A., Asenbaum, S., Tauscher, J. T., Fuchs, K., Sieghart, W., Hornik, K., et al. (2001) · Biological Psychiatry · doi:10.1016/s0006-3223(00)01123-9 · Cited by 120 · see citing works
Alternative Splicing of the Human Serotonin Transporter Gene
Bradley, C. C., & Blakely, R. (1997) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1997.69041356.x · Cited by 111 · see citing works
Functional analysis of a novel human serotonin transporter gene promoter in immortalized raphe cells
Mortensen, O. V., Thomassen, M., Larsen, M. B., Whittemore, S. R., & Wiborg, O. (1999) · Molecular Brain Research · doi:10.1016/s0169-328x(99)00083-2 · Cited by 97 · see citing works
Jönsson, E. G., Nöthen, M. M., Gustavsson, P. J., Neidt, H., Bunzel, R., Propping, P., & Sedvall, G. C. (1998) · Psychiatry Research · doi:10.1016/s0165-1781(98)00027-4 · Cited by 96 · see citing works
Kaiser, R., Tremblay, P.-B., Schmider, J., Henneken, M., Dettling, M., Müller-Oerlinghausen, B., Uebelhack, R., Roots, I., & Brockmöller, J. (2001) · Molecular Psychiatry · doi:10.1038/sj.mp.4000821 · Cited by 95 · see citing works
Battersby, S., Ogilvie, A. D., Blackwood, D., Shen, S., Muqit, M. M. K., Muir, W. J., Teague, P., Goodwin, G. M., & Harmar, A. J. (1999) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1999.721384.x · Cited by 93 · see citing works
Mowry, B. J., & Nancarrow, D. (2001) · Clinical and Experimental Pharmacology and Physiology · doi:10.1046/j.1440-1681.2001.03399.x · Cited by 89 · see citing works
Kaiser, R., Müller-Oerlinghausen, B., Filler, D., Tremblay, P., Berghöfer, A., Roots, I., & Brockmöller, J. (2002) · American Journal of Medical Genetics · doi:10.1002/ajmg.10119 · Cited by 87 · see citing works
Nobile, M., Begni, B., Giorda, R., Frigerio, A., Marino, C., Molteni, M., Ferrarese, C., & Battaglia, M. (1999) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1097/00004583-199911000-00014 · Cited by 77 · see citing works
Lesch, K. (2001) · European Neuropsychopharmacology · doi:10.1016/s0924-977x(01)00123-7 · Cited by 67 · see citing works
Molecular genetics of schizophrenia: past, present and future
Prasad, S., Semwal, P., Deshpande, S. N., Triptish Bhatia, A., LNimgaonkar, V., & Thelma, B. K. (2002) · Journal of Biosciences · doi:10.1007/bf02703682 · Cited by 59 · see citing works
Liu, W., Gu, N., Feng, G., Li, S., Bai, S., Zhang, J., Shen, T., Xue, H., Breen, G. D., Clair, D. S., et al. (1999) · PubMed · Cited by 55 · see citing works
Stöber, G., Jatzke, S., Heils, A., et al. (1998) · European Archives of Psychiatry and Clinical Neuroscience · doi:10.1007/s004060050022 · Cited by 55 · see citing works
Hranilović, D., Schwab, S. G., Jernej, B., et al. (2000) · Molecular Psychiatry · doi:10.1038/sj.mp.4000599 · Cited by 52 · see citing works
Self-citationHernandez, A. I., & Sokolov, B. P. (1997) · Molecular Psychiatry · doi:10.1038/sj.mp.4000215 · Cited by 52 · see citing works
Naylor, L., Dean, B., Opeskin, K., et al. (1996) · Journal of Neural Transmission · doi:10.1007/bf01271234 · Cited by 49 · see citing works
Modified structure of the human serotonin transporter promoter
Flattem, N. L., & Blakely, R. (2000) · Molecular Psychiatry · doi:10.1038/sj.mp.4000585 · Cited by 49 · see citing works
Naylor, L., Dean, B., Pereira, A. M., Mackinnon, A. J., Kouzmenko, A., & Copolov, D. (1998) · Molecular Medicine · doi:10.1007/bf03401928 · Cited by 47 · see citing works
The silencer activity of the novel human serotonin transporter linked polymorphic regions
Sakai, K., Nakamura, M., Ueno, S., Sano, A., Sakai, N., Shirai, Y., & Saito, N. (2002) · Neuroscience Letters · doi:10.1016/s0304-3940(02)00348-8 · Cited by 40 · see citing works
Serotonin transporter gene is not associated with symptomatology of schizophrenia
Serretti, A., Catalano, M., & Smeraldi, E. (1999) · Schizophrenia Research · doi:10.1016/s0920-9964(98)00111-x · Cited by 33 · see citing works
Serotonin transporter gene polymorphism and schizophrenia: An association study
Bonnet‐Brilhault, F., Laurent‐Levinson, C., Thibaut, F., et al. (1997) · Biological Psychiatry · doi:10.1016/s0006-3223(97)00320-x · Cited by 31 · see citing works
Behavioral phenotypes: Conceptual and methodological issues
Flint, J. (1998) · American Journal of Medical Genetics · doi:10.1002/(sici)1096-8628(19980508)81:3 · Cited by 28 · see citing works
Schizophrenia and the serotonin transporter gene
Rao, D. C., Jönsson, E. G., Paus, S., et al. (1998) · Psychiatric Genetics · doi:10.1097/00041444-199808040-00002 · Cited by 28 · see citing works
Functionally gene-linked polymorphic regions and genetically controlled neurotransmitters metabolism
Catalano, M. (2001) · European Neuropsychopharmacology · doi:10.1016/s0924-977x(01)00120-1 · Cited by 22 · see citing works
Tsai, S., Ouyang, W., & Hong, C. (2002) · Neuropsychobiology · doi:10.1159/000054952 · Cited by 17 · see citing works
Herken, H. (2002) · Schizophrenia Research · doi:10.1016/s0920-9964(01)00391-7 · Cited by 8 · see citing works
Kallmann syndrome gene (KAL-X) is not mutated in schizophrenia
O’Neill, M. J., Brewer, W. J., Thornley, C., Copolov, D., Warne, G. L., Sinclair, A. H., Forrest, S., & Williamson, R. (1999) · American Journal of Medical Genetics · doi:10.1002/(sici)1096-8628(19990205)88:1 · Cited by 7 · see citing works
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Serretti, A., Kato, M., De Ronchi, D., & Kinoshita, T. (2007) · Molecular Psychiatry · doi:10.1038/sj.mp.4001926 · Cited by 529 · see citing works
Philibert, R. A., Sandhu, H., Hollenbeck, N., Gunter, T., Adams, W., & Madan, A. (2008) · American Journal of Medical Genetics Part B: Neuropsychiatric Genetics · doi:10.1002/ajmg.b.30657 · Cited by 300 · see citing works
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Parsey, R. V., Hastings, R. S., Oquendo, M. A., Hu, X., Goldman, D., Huang, Y.-Y., Simpson, N., Arcement, J., Huang, Y., Ogden, R. T., et al. (2006) · American Journal of Psychiatry · doi:10.1176/appi.ajp.163.1.48 · Cited by 262 · see citing works
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Beitchman, J. H., Baldassarra, L., Mik, H., De Luca, V., King, N., Bender, D., Ehtesham, S., & Kennedy, J. L. (2006) · American Journal of Psychiatry · doi:10.1176/ajp.2006.163.6.1103 · Cited by 167 · see citing works
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Kinnally, E. L., Capitanio, J. P., Leibel, R., Deng, L., LeDuc, C., Haghighi, F., & Mann, J. J. (2010) · Genes, Brain and Behavior · doi:10.1111/j.1601-183x.2010.00588.x · Cited by 155 · see citing works
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Binder, E. B., Jeffrey Newport, D., Zach, E. B., Smith, A. K., Deveau, T. C., Altshuler, L. L., Cohen, L. S., Stowe, Z. N., & Cubells, J. F. (2010) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2009.12.001 · Cited by 69 · see citing works
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- Authors
- Hranilovic, D., Stefulj, J., Schwab, S., Borrmann-Hassenbach, M., Albus, M., Jernej, B., & Wildenauer, D.
- Affiliations
- University of Bonn (DE)
- Ruđer Bošković Institute (HR)
- Corresponding author
- Jernej, Branimir
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2004-06
- Volume
- 55
- Issue
- 11
- Pages
- 1090-1094
- ISSN
- 0006-3223 (ISSN-L)
- OpenAlex
- W2011793525
- Cited by
- 224
- References
- 48
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 1 · 2023: 2 · 2022: 1 · 2021: 5 · 2020: 3 · 2019: 5 · 2018: 9 · 2017: 3 · 2016: 6 · 2015: 5 · 2014: 11 · 2013: 11 · 2012: 14
- FWCI
- 5.87
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Bundesministerium für Bildung und Forschung
- Ministry of Science and Technology, Croatia
- Deutsche Forschungsgemeinschaft (400)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Keywords
- serotonin transporter, serotonin transporter gene, 5-HTTLPR, promoter polymorphism, variable number tandem repeats, gene expression, mRNA levels, schizophrenia, family-based association, lymphoblastoid cell lines
- MeSH terms
- Adult, Analysis of Variance, Carrier Proteins, Family Health, Female, Genotype, Humans, Lymphocytes, Male, Membrane Glycoproteins, Nerve Tissue Proteins, Polymorphism, Genetic, Promoter Regions, Genetic, RNA, Messenger, Schizophrenia, Gene Expression, Minisatellite Repeats, Reverse Transcriptase Polymerase Chain Reaction, Membrane Transport Proteins, Serotonin Plasma Membrane Transport Proteins
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