DTNBP1 Gene Is Associated with Some Symptom Factors of Schizophrenia in Chinese Han Nationality

doi:10.1016/S1001-9294(10)60027-2

Abstract

Abstract: Objective To study the association of DTNBP1 gene with some symptom factors of schizophrenia.Methods A total of 285 unrelated schizophrenic individuals were recruited from December 2004 to January 2009 for genetic analysis, and their symptom factors were assessed based on the Positive and Negative Syndrome Scale (PANSS). The quantitative trait test was performed by the UNPHASED program (version 3.0.12) to investigate the association between scored positive and negative symptoms and the single nucleotide polymorphisms (SNPs) in DTNBP1 gene.Results The quantitative trait test showed allelic association of rs909706 with the excitement symptom of schizophrenia (P<0.05, adjusted by 10 000 permutations), while the genotype C/G of rs2619539 with a negative symptom, lack of spontaneity and flow of conversation (P<0.05, adjusted by 10 000 permutations).Conclusion DTNBP1 variations are possibly associated with some symptoms of schizophrenia, which could partly explain the relationship between the susceptibility gene DTNBP1 and that disease.

Key words: schizophrenia, DTNBP1 gene, positive and negative symptoms, quantitative trait test

Funding:

Supported by National High Technology Research and Develo- pment Program of China (863 Program) (2006AA02A407), Na- tional Basic Research Program (973 Program) (2010CB529603), and Beijing Natural Science Foundation (7102109)

Yu-hui Sun, Yan Shen and Qi Xu. DTNBP1 Gene Is Associated with Some Symptom Factors of Schizophrenia in Chinese Han Nationality[J].Chinese Medical Sciences Journal, 2010, 25(2): 85-89.

References 32

1.	Kay SR, Fiszbein A, Opler LA. The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophr Bull 1987; 13:261-76.
2.	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; 71:337-48.
3.	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; 72:185-90.
4.	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; 55:971-5.
5.	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; 61:336-44.
6.	De Luca V, Voineskos D, Shinkai T, et al. Untranslated region haplotype in dysbindin gene: analysis in schizophrenia. J Neural Transm 2005; 112:1263-7.
7.	Li T, Zhang F, Liu X, et al. Identifying potential risk haplotypes for schizophrenia at the DTNBP1 locus in Han Chinese and Scottish populations. Mol Psychiatry 2005; 10:1037-44.
8.	Duan J, Martinez M, Sanders AR, et al. DTNBP1 (Dystrobrevin binding protein 1) and schizophrenia: association evidence in the 3' end of the gene. Hum Hered 2007; 64:97-106.
9.	Riley B, Kuo PH, Maher BS, et al. The dystrobrevin binding protein 1 (DTNBP1) gene is associated with schizophrenia in the Irish Case Control Study of Schizophrenia (ICCSS) sample. Schizophr Res 2009; 115:245-53.
10	Zuo L, Luo X, Kranzler HR, et al. Association study of DTNBP1 with schizophrenia in a US sample. Psychiatr Genet 2009; 19:292-304.
11	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; 61:544-55.
12	Bray NJ, Preece A, Williams NM, et al. Haplotypes at the dystrobrevin binding protein 1 (DTNBP1) gene locus mediate risk for schizophrenia through reduced DTNBP1 expression. Hum Mol Genet 2005; 14:1947-54.
13	Weickert CS, Rothmond DA, Hyde TM, et al. Reduced DTNBP1 (dysbindin-1) mRNA in the hippocampal formation of schizophrenia patients. Schizophr Res 2008; 98: 105-10.
14	Tang J, LeGros RP, Louneva N, et al. Dysbindin-1 in dorsolateral prefrontal cortex of schizophrenia cases is reduced in an isoform-specific manner unrelated to dysbindin-1 mRNA expression. Hum Mol Genet 2009; 18: 3851-63.
15	Morris DW, McGhee KA, Schwaiger S, et al. No evidence for association of the dysbindin gene [DTNBP1] with schizophrenia in an Irish population-based study. Schi- zophr Res 2003; 60:167-72.
16	Datta SR, McQuillin A, Puri V, et al. Failure to confirm allelic and haplotypic association between markers at the chromosome 6p22.3 dystrobrevin-binding protein 1 (DTNBP1) locus and schizophrenia. Behav Brain Funct 2007; 3:50.
17	Liu CM, Liu YL, Fann CS, et al. No association evidence between schizophrenia and dystrobrevin-binding protein 1 (DTNBP1) in Taiwanese families. Schizophr Res 2007; 93:391-8.
18	Peters K, Wiltshire S, Henders AK, et al. Comprehensive analysis of tagging sequence variants in DTNBP1 shows no association with schizophrenia or with its composite neurocognitive endophenotypes. Am J Med Genet B Neuropsychiatr Genet 2008; 147B:1159-66.
19	Burdick KE, Goldberg TE, Funke B, et al. DTNBP1 genotype influences cognitive decline in schizophrenia. Schi- zophr Res 2007; 89:169-72.
20	Donohoe G, Morris DW, Clarke S, et al. Variance in neurocognitive performance is associated with dysbindin-1 in schizophrenia: a preliminary study. Neuropsychologia 2007; 45:454-8.
21	Zinkstok JR, de Wilde O, van Amelsvoort, et al. Association between the DTNBP1 gene and intelligence: a case-control study in young patients with schizophrenia and related disorders and unaffected siblings. Behav Brain Funct 2007; 3:19.
22	Hashimoto R, Noguchi H, Hori H, et al. A genetic variation in the dysbindin gene (DTNBP1) is associated with memory performance in healthy controls. World J Biol Psychiatry 2010; 11:431-8.
23	Hashimoto R, Noguchi H, Hori H, et al. Association between the dysbindin gene (DTNBP1) and cognitive functions in Japanese subjects. Psychiatry Clin Neurosci 2009; 63:550-6.
24	Luciano M, Miyajima F, Lind PA, et al. Variation in the dysbindin gene and normal cognitive function in three independent population samples. Genes Brain Behav 2009; 8:218-27.
25	Narr KL, Szeszko PR, Lencz T, et al. DTNBP1 is associated with imaging phenotypes in schizophrenia. Hum Brain Mapp 2009; 30:3783-94.
26	Wolf C, Jackson MC, Kissling C, et al. Dysbindin-1 genotype effects on emotional working memory. Mol Psychiatry 2009 [Epub ahead of print].
27	Pae CU, Drago A, Kim JJ, et al. DTNBP1 haplotype influences baseline assessment scores of schizophrenic in-patients. Neurosci Lett 2008; 440:150-4.
28	Zuo L, Luo X, Krystal JH, et al. The efficacies of clozapine and haloperidol in refractory schizophrenia are related to DTNBP1 variation. Pharmacogenet Genomics 2009; 19:437-46.
29	Dudbridge F. Pedigree disequilibrium tests for multilocus haplotypes. Genet Epidemiol 2003; 25:115-21.
30	Fanous AH, Kendler KS. Genetic heterogeneity, modifier genes, and quantitative phenotypes in psychiatric illness: searching for a framework. Mol Psychiatry 2005; 10:6-13.
31	Kishimoto M, Ujike H, Motohashi Y, et al. The dysbindin gene (DTNBP1) is associated with methamphetamine psychosis. Biol Psychiatry 2008; 63:191-6.
32	Corvin A, Donohoe G, Nangle JM, et al. A dysbindin risk haplotype associated with less severe manic-type symptoms in psychosis. Neurosci Lett 2008; 431:146-9.

Early edition

Current issue

Archive

Specialties & Topics

Author center

Reviewer center