Skip to main content Accessibility help

Association of P1635 and P1655 polymorphisms in dysbindin (DTNBP1) gene with schizophrenia

  • Fatemeh Alizadeh (a1), Mohammad Amin Tabatabaiefar (a1) (a2), Mohammad Ghadiri (a3), Mir Saeed Yekaninejad (a4), Nazanin Jalilian (a1) and Mohammad Reza Noori-Daloii (a1)...


Objectives: Schizophrenia (SCZ) is a severe psychiatric disorder with a lifetime prevalence of approximately 1% in most of the populations studied. SCZ is multifactorial with the contribution of multiple susceptibility genes that could act in conjunction with epigenetic processes and environmental factors. There is some evidence supporting the association between genetic variants in dysbindin (DTNBP1) gene and SCZ in populations. In this study, we investigated the association between polymorphisms P1635 and P1655 in dysbindin gene with SCZ.

Methods: Totally, 115 unrelated patients with SCZ and 117 unrelated healthy volunteers were studied. Genomic DNA was extracted from blood. Genotyping was done with the PCR-RFLP method. The allele and genotype associations were analysed with X2 test. The Benjamini-Hochberg procedure was used to correct p values for multiple comparisons.

Results: The results showed no significant difference between patients and controls in allelic frequencies or genotypic distributions of SNP P1635 (p = 0.809), but a significant difference between the case and control groups for SNP P1655 (p = 0.009) was found. We could also find a significant positive association between A-C haplotype and SCZ (OR = 1.7, 95% CI 1.18–2.42; p = 0.004, pc = 0.02) and a protective effect for A-G haplotype (p = 0.003, OR = 0.57, 95% CI 1.18–2.42; p = 0.003, pc = 0.02).

Conclusion: This study may provide further support for the association between SNP polymorphisms in DTNBP1 and SCZ in the Iranian population. Studies with more markers and subjects for various populations will be necessary to understand the genetic contribution of the gene to the development of SCZ.


Corresponding author

M.R. Noori-Daloii, Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Poursina Ave, 16 Azar St. Keshavarz BLVD, Tehran 1417613151, Iran. Tel: +98(21)88953005; Fax: +98(21)88953005; E-mail:


Hide All
1.Karayiorgou, M, Gogos, JA.A turning point in schizophrenia genetics. Neuron 1997;19:967979.
2.Hanson, DR, Gottesman, II.Theories of schizophrenia: a genetic-inflammatory-vascular synthesis. BMC Med Genet 2005;6:7.
3.Gogos, JA, Gerber, DJ.Schizophrenia susceptibility genes: emergence of positional candidates and future directions. Trends Pharmacol Sci 2006;27:226233.
4.Iizuka, Y, Sei, Y, Weinberger, DR, Straub, RE.Evidence that the BLOC-1 protein dysbindin modulates dopamine D2 receptor internalization and signaling but not D1 internalization. J Neurosci 2007;27:1239012395.
5.Li, D, He, L.Association study between the dystrobrevin binding protein 1 gene (DTNBP1) and schizophrenia: a meta-analysis. Schizophr Res 2007;96:112118.
6.Owen, MJ, Craddock, N, Jablensky, A.The genetic deconstruction of psychosis. Schizophr Bull 2007;33:905911.
7.Harrison, PJ, Owen, MJ.Genes for schizophrenia? Recent findings and their pathophysiological implications. Lancet 2003;361:417419.
8.Veroni, C, Grasso, M, Macchia, G, Ramoni, C, Ceccarini, M, Petrucci, TC, Macioce, P.Beta-dystrobrevin, a kinesin-binding receptor, interacts with the extracellular matrix components pancortins. J Neurosci Res 2007;85:26312639.
9.Benson, MA, Newey, SE, Martin-Rendon, E, Hawkes, R, Blake, DJ.Dysbindin, a novel coiled-coil-containing protein that interacts with the dystrobrevins in muscle and brain. J Biol Chem 2001;276:2423224241.
10.Pimm, J, McQuillin, A, Thirumalai, S, et al. The Epsin 4 gene on chromosome 5q, which encodes the clathrin-associated protein enthoprotin, is involved in the genetic susceptibility to schizophrenia. Am J Hum Genet 2005;76: 902907.
11.Nazarian, R, Starcevic, M, Spencer, MJ, Dell'Angelica, EC.Reinvestigation of the dysbindin subunit of BLOC-1 (biogenesis of lysosome-related organelles complex-1) as a dystrobrevin-binding protein. Biochem J 2006;395: 587598.
12.Knuesel, I, Mastrocola, M, Zuellig, RA, Bornhauser, B, Schaub, MC, Fritschy, JM.Short communication: altered synaptic clustering of GABAA receptors in mice lacking dystrophin (mdx mice). Eur J Neurosci 1999;11:44574462.
13.Krystal, JH, Sanacora, G, Blumberg, H, et al. Glutamate and GABA systems as targets for novel antidepressant and mood-stabilizing treatments. Mol Psychiatry 2002;7(Suppl. 1):S71S80.
14.D'Sa, C, Duman, RS.Antidepressants and neuroplasticity. Bipolar Disord 2002;4:183194.
15.McLeod, TM, Lopez-Figueroa, AL, Lopez-Figueroa, MO.Nitric oxide, stress, and depression. Psychopharmacol Bull 2001;35:2441.
16.Brambilla, P, Perez, J, Barale, F, Schettini, G, Soares, JC.GABAergic dysfunction in mood disorders. Mol Psychiatry 2003;8:721737.
17.Duman, RS, Malberg, J, Nakagawa, S, D'Sa, C.Neuronal plasticity and survival in mood disorders. Biol Psychiatry 2000;48:732739.
18.Straub, RE, Jiang, Y, MacLean, CJ, et al. Genetic variation in the 6p22.3 gene DTNBP1, the human ortholog of the mouse dysbindin gene, is associated with schizophrenia. Am J Hum Genet 2002;71:337348.
19.Schwab, SG, Knapp, M, Mondabon, S, et al. Support for association of schizophrenia with genetic variation in the 6p22.3 gene, dysbindin, in sib-pair families with linkage and in an additional sample of triad families. Am J Hum Genet 2003;72:185190.
20.Tang, JX, Zhou, J, Fan, JB, et al. Family-based association study of DTNBP1 in 6p22.3 and schizophrenia. Mol Psychiatry 2003;8:717718.
21.Kirov, G, Ivanov, D, Williams, NM, et al. Strong evidence for association between the dystrobrevin binding protein 1 gene (DTNBP1) and schizophrenia in 488 parent-offspring trios from Bulgaria. Biol Psychiatry 2004;55:971975.
22.De Luca, V, Voineskos, D, Shinkai, T, Wong, G, Kennedy, JL.Untranslated region haplotype in dysbindin gene: analysis in schizophrenia. J Neural Transm 2005;112: 12631267.
23.Van Den Bogaert, A, Schumacher, J, Schulze, TG, et al. The DTNBP1 (dysbindin) gene contributes to schizophrenia, depending on family history of the disease. Am J Hum Genet 2003;73:14381443.
24.Kishimoto, M, Ujike, H, Motohashi, Y, et al. The dysbindin gene (DTNBP1) is associated with methamphetamine psychosis. Biol Psychiatry 2008;63:191196.
25.Benjamini, Y, Hochberg, Y.Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc B (Methodological) 1995;57:289300.
26.Benjamini, Y, Krieger, AM, Yekutieli, D.Adaptive linear step-up procedures that control the false discovery rate. Biometrika 2006;93:491507.
27.Stephens, M, Smith, NJ, Donnelly, P.A new statistical method for haplotype reconstruction from population data. Am J Hum Genet 2001;68:978989.
28.Tochigi, M, Zhang, X, Ohashi, J, et al. Association study of the dysbindin (DTNBP1) gene in schizophrenia from the Japanese population. Neurosci Res 2006;56: 154158.
29.Joo, EJ, Lee, KY, Jeong, SH, Ahn, YM, Koo, YJ, Kim, YS.The dysbindin gene (DTNBP1) and schizophrenia: no support for an association in the Korean population. Neurosci Lett 2006;407:101106.
30.Galehdari, H, Ajam, T, Pooryasin, A, Foroughmand, AM, Kazeminejad, SR.Combined effect of polymorphic sites in the DTNBP1 and GRIN1 genes on schizophrenia. MJIRI 2010;24:510.
31.Tosato, S, Ruggeri, M, Bonetto, C, et al. Association study of dysbindin gene with clinical and outcome measures in a representative cohort of Italian schizophrenic patients. Am J Med Genet B Neuropsychiatr Genet 2007;144B:647659.
32.Williams, NM, Preece, A, Morris, DW, et al. Identification in 2 independent samples of a novel schizophrenia risk haplotype of the dystrobrevin binding protein gene (DTNBP1). Arch Gen Psychiatry 2004;61:336344.
33.Bray, NJ, Preece, A, Williams, NM, Moskvina, V, Buckland, PR, Owen, MJ, O'Donovan, MC.Haplotypes at the dystrobrevin binding protein 1 (DTNBP1) gene locus mediate risk for schizophrenia through reduced DTNBP1 expression. Hum Mol Genet 2005;14:19471954.
34.Numakawa, T, Yagasaki, Y, Ishimoto, T, et al. Evidence of novel neuronal functions of dysbindin, a susceptibility gene for schizophrenia. Hum Mol Genet 2004;13: 26992708.
35.Talbot, K, Eidem, WL, Tinsley, CL, et al. Dysbindin-1 is reduced in intrinsic, glutamatergic terminals of the hippocampal formation in schizophrenia. J Clin Invest 2004;113:13531363.
36.Weickert, CS, Straub, RE, McClintock, BW, et al. Human dysbindin (DTNBP1) gene expression in normal brain and in schizophrenic prefrontal cortex and midbrain. Arch Gen Psychiatry 2004;61:544555.
Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

Acta Neuropsychiatrica
  • ISSN: 0924-2708
  • EISSN: 1601-5215
  • URL: /core/journals/acta-neuropsychiatrica
Please enter your name
Please enter a valid email address
Who would you like to send this to? *



Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed