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Neurogenic locus notch homolog protein 4 and brain-derived neurotrophic factor variants combined effect on schizophrenia susceptibility

Published online by Cambridge University Press:  01 May 2013

Xue-xi Yang ,
An-na Zhu ,
Fen-xia Li ,
Zhong-xiang Zhang  and
Ming Li
Xue-xi Yang
Affiliation:
School of Biotechnology, Southern Medical University, Guangzhou, Guangdong, China
An-na Zhu
Affiliation:
School of Biotechnology, Southern Medical University, Guangzhou, Guangdong, China
Fen-xia Li
Affiliation:
Research Institute of Da An Gene Co., Ltd, Sun Yat-sen University, Guangzhou, Guangdong, China
Zhong-xiang Zhang
Affiliation:
Research Institute of Da An Gene Co., Ltd, Sun Yat-sen University, Guangzhou, Guangdong, China
Ming Li*
Affiliation:
School of Biotechnology, Southern Medical University, Guangzhou, Guangdong, China
*
Ming Li, Professor, School of Biotechnology, Southern Medical University, Guangzhou 510515, P.R. China. Tel: +86 20 61648550; Fax: +86 20 61648554; E-mail: [email protected]
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Abstract

Objectives

To investigate the relationships between single-nucleotide polymorphisms (SNPs) in NOTCH4 and brain-derived neurotrophic factor (BDNF) with schizophrenia among Han Chinese in Southern China.

Methods

Two NOTCH4 SNPs (rs520688 and rs415929) and two BDNF SNPs (rs2030324 and rs12273539) were examined in 464 schizophrenics and 464 healthy controls from Hunan province in South China, using the Sequenom MassARRAY® iPLEX System.

Results

In the study population, rs520688 and rs2030324 were significantly associated with schizophrenia. A decreased risk of schizophrenia was associated with the rs520688 GA genotype (p = 0.035), whereas an increased risk of schizophrenia was associated with the rs2030324 CC/CT genotype (p = 0.044). The genotype distributions of rs415929 in NOTCH4 and rs12273539 in BDNF did not differ significantly between the case and control groups. Although no allele–allele interactions were detected between rs520688 and rs2030324, recombination analysis revealed a combined effect of the two on the susceptibility to schizophrenia, with GA-TT decreasing and CT/CC-GG/GA increasing the risk of schizophrenia.

Conclusion

In conclusion, rs520688 in NOTCH4 and rs2030324 in BDNF are significantly associated with schizophrenia among Han Chinese in Southern China. The two had a combined effect on the susceptibility to schizophrenia among Han Chinese in Southern China, but this may not be caused by an allele–allele interaction.

Keywords

BDNFNOTCH4schizophreniaSNPsusceptibility
Type
Original Articles
Information
Acta Neuropsychiatrica , Volume 25 , Issue 6 , December 2013 , pp. 356 - 360
Copyright
Copyright © Scandinavian College of Neuropsychopharmacology 2013 

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Footnotes

†

These authors contributed equally to this work.

References

1.Eaton, WW. Update on the epidemiology of schizophrenia. Epidemiol Rev 1991;13:320–328.CrossRefGoogle ScholarPubMed
2.Sartorius, N, Jablensky, A, Korten, Aet al. Early manifestation and first contact incidence of schizophrenia in different cultures. Psychol Med 1986;16:909–928.CrossRefGoogle ScholarPubMed
3.Cardno, AG, Gottesman, II. Twin studies of SCZ: from bow-and-arrow concordances to star wars Mx and functional genomics. Am J Med Genet 2000;97:12–17.3.0.CO;2-U>CrossRefGoogle Scholar
4.Sullivan, PF, Kendler, KS, Neale, MC. SCZ as a complex trait: evidence from a meta-analysis of twin studies. Arch Gen Psychiatry 2003;60:1187–1192.CrossRefGoogle Scholar
5.Ripke, S, Sanders, AR, Kendler, KSet al. Genome-wide association study identifies five new schizophrenia loci. Nat Genet 2011;43:969–976.Google Scholar
6.Wei, J, Hemmings, GP. The Notch4 locus is associated with susceptibility to schizophrenia. Nat Genet 2000;25:376–377.CrossRefGoogle ScholarPubMed
7.Glatt, SJ, Wang, RS, Yeh, YC, Tsuang, MT, Faraone, SV. Five NOTCH4 polymorphisms show weak evidence for association with schizophrenia: evidence from meta-analyses. Schizophr Res 2005;73:281–290.CrossRefGoogle ScholarPubMed
8.Luo, X, Klempan, TA, Lappalainen, Jet al. NOTCH4 gene haplotype is associated with schizophrenia in African Americans. Biol Psychiatry 2004;55:112–117.CrossRefGoogle ScholarPubMed
9.Shibata, N, Ohnuma, T, Hiqashi, Set al. Genetic association between Notch4 polymorphisms and Japanese schizophrenics. Psychiatr Gen 2006;16:77–79.CrossRefGoogle ScholarPubMed
10.Yi, Z, Zhang, C, Wu, Zet al. Lack of effect of brain derived neurotrophic factor (BDNF) Val66Met polymorphism on early onset schizophrenia in Chinese Han population. Brain Res 2011;1417:146–150.CrossRefGoogle ScholarPubMed
11.Watanabe, Y, Nunokawa, A, Kaneko, N, Someya, T. Meta-analysis of case–control association studies between the C270T polymorphism of the brain-derived neurotrophic factor gene and schizophrenia. Schizophr Res 2007;95:250–252.CrossRefGoogle ScholarPubMed
12.Ikeda, M, Aleksic, B, Kinoshita, Yet al. Genome-wide association study of schizophrenia in a Japanese population. Biol Psychiatry 2011;69:472–478.CrossRefGoogle Scholar
13.Durany, N, Michel, T, Zöchling, Ret al. Brain-derived neurotrophic factor and neurotrophin in schizophrenic psychoses. Schizophr Res 2001;52:79–86.CrossRefGoogle ScholarPubMed
14.Pedrini, M, Chendo, I, Grande, Iet al. Serum brain-derived neurotrophic factor and clozapine daily dose in patients with schizophrenia: a positive correlation. Neurosci Lett 2011;491:207–210.CrossRefGoogle ScholarPubMed
15.Favalli, G, Li, J, Belmonte-de-Abreu, P, Wong, AH, Daskalakis, ZJ. The role of BDNF in the pathophysiology and treatment of schizophrenia. J Psychiatr Res 2012;46:1–11.CrossRefGoogle ScholarPubMed
16.Pierri, JN, Volk, CL, Auh, S, Sampson, A, Lewis, DA. Somal size of prefrontal cortical pyramidal neurons in schizophrenia; differential effects across neuronal subpopulations. Biol Psychiatry 2003;54:111–120.CrossRefGoogle ScholarPubMed
17.Krebs, LT, Xue, Y, Norton, CRet al. Notch signaling is essential for vascular morphogenesis in mice. Genes Dev 2000;14:1343–1352.CrossRefGoogle ScholarPubMed
18.Lee, J, Duan, W, Mattson, MP. Evidence that brain-derived neurotrophic factor is required for basal neurogenesis and mediates, in part, the enhancement of neurogenesis by dietary restriction in the hippocampus of adult mice. J Neurochem 2002;82:1367–1375.CrossRefGoogle ScholarPubMed
19.Barnabé-Heider, F, Miller, FD. Endogenously produced neurotrophins regulate survival and differentiation of cortical progenitors via distinct signaling pathways. J Neurosci 2003;23:5149–5160.CrossRefGoogle ScholarPubMed
20.Cheng, A, Wang, S, Cai, J, Rao, MS, Mattson, MP. Nitric oxide acts in a positive feedback loop with BDNF to regulate neural progenitor cell proliferation and differentiation in the mammalian brain. Dev Biol 2003;258:319–333.CrossRefGoogle Scholar
21.Louissaint, JA, Rao, S, Leventhal, C, Goldman, SA. Coordinated interaction of neurogenesis and angiogenesis in the adult songbird brain. Neuron 2002;34:945–960.CrossRefGoogle ScholarPubMed
22.Larsson, E, Nanobashvili, A, Kokaia, Z, Lindvall, O. Evidence for neuroprotective effects of endogenous brain-derived neurotrophic factor after global forebrain ischemia in rats. J Cereb Blood Flow Metab 1999;19:1220–1228.CrossRefGoogle ScholarPubMed
23.Benes, FM. Neurobiological investigations in cingulate cortex of schizophrenic brain. Schizophr Bull 1993;19:537–549.CrossRefGoogle ScholarPubMed
24.Garey, L. When cortical development goes wrong: schizophrenia as a neurodevelopmental disease of microcircuits. J Anat 2010;217:324–333.CrossRefGoogle ScholarPubMed
25.Fatemi, SH, Folsom, TD. The neurodevelopmental hypothesis of schizophrenia, revisited. Schizophr Bull 2009;35:528–548.CrossRefGoogle ScholarPubMed
26.Benes, FM, Todtenkopf, MS, Taylor, JB. Differential distribution of tyrosine hydroxylase fibers on small and large neurons in layer II of anterior cingulate cortex of schizophrenic brain. Synapse 1997;25:80–92.3.0.CO;2-2>CrossRefGoogle ScholarPubMed
27.Schmidt-Kastner, R, Van Os, J, Wm Steinbusch, H, Schmitz, C. Gene regulation by hypoxia and the neurodevelopmental origin of schizophrenia. Schizophr Res 2006;84:253–271.CrossRefGoogle ScholarPubMed
28.Glantz, LA, Gilmore, JH, Lieberman, JA, Jarskog, LF. Apoptotic mechanisms and the synaptic pathology of schizophrenia. Schizophr Res 2006;81:47–63.CrossRefGoogle ScholarPubMed
29.Honig, LS, Rosenberg, RN. Apoptosis and neurologic disease. Am J Med 2000;108:317–330.CrossRefGoogle ScholarPubMed