Association between 5q23.2-located polymorphism of CTXN3 gene (Cortexin 3) and schizophrenia in European-Caucasian males; implications for the aetiology of schizophrenia

Behavioral and Brain Functions

Omar Šerý⁴  Jan Lochman³  Jana Povová²  Vladimír Janout²  Jiří Plesník³  Vladimir J Balcar¹ 

[1] Laboratory of Neurochemistry, Bosch Institute and Discipline of Anatomy and Histology, School of Medical Sciences, Sydney Medical School, The University of Sydney, Sydney, 2006, NSW, AUSTRALIA

[2] Department of Epidemiology and Public Health, Faculty of Medicine, University of Ostrava, Ostrava, Czech Republic

[3] Laboratory of Neurobiology and Molecular Psychiatry, Laboratory of Molecular Physiology, Department of Biochemistry, Faculty of Science, Masaryk University, Kotlářská 2, 611 37, Brno, Czech Republic

[4] Institute of Animal Physiology and Genetics, Academy of Sciences, Veveří 97, 602 00, Brno, Czech Republic

关键词: Alzheimer’s disease;    Amyloid precursor protein (APP);    GABAergic neurotransmission;    NKCC1;    SLC12A2;    DISC1;   

Others  :  1139058
DOI  :  10.1186/s12993-015-0057-9

 received in 2014-09-19, accepted in 2015-03-02,  发布年份 2015

【 摘 要 】

Background

The objective of the study was to examine several polymorphisms in DISC1 and CTNX3 genes as possible risk factors in schizophrenia. DISC1 (disrupted-in-schizophrenia 1) has been studied extensively in relation to mental disease while CTXN3, has only recently emerged as a potential “candidate” gene in schizophrenia. CTXN3 resides in a genomic region (5q21-34) known to be associated with schizophrenia and encodes a protein cortexin 3 which is highly enriched in brain.

Methods

We used ethnically homogeneous samples of 175 male patients and 184 male control subjects. All patients were interviewed by two similarly qualified psychiatrists. Controls were interviewed by one of the authors (O.S.). Genotyping was performed, following amplification by polymerase chain reaction (PCR), using fragment analysis in a standard commercial setting (Applied Biosystems, USA).

Results

We have found a statistically significant association between rs6595788 polymorphism of CTXN3 gene and the risk of schizophrenia; the presence of AG genotype increased the risk 1.5-fold. Polymorphisms in DISC1 gene showed only marginally statistically significant association with schizophrenia (rs17817356) or no association whatsoever (rs821597 and rs980989) while two polymorphisms (rs9661837 and rs3737597) were found to be only slightly polymorphic in the samples.

Conclusion

Evidence available in the literature suggests that altered expression of cortexin 3, either alone, or in parallel with changes in DISC1, could subtly perturb GABAergic neurotransmission and/or metabolism of amyloid precursor protein (APP) in developing brain, thus potentially exposing the affected individual to an increased risk of schizophrenia later in life.

【 授权许可】

   
2015 Šerý et al.; licensee BioMed Central.

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