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Association study of polymorphisms in synaptic vesicle-associated genes, SYN2 and CPLX2, with schizophrenia.

ABSTRACT: BACKGROUND: The occurrence of aberrant functional connectivity in the neuronal circuit is one of the integrative theories of the etiology of schizophrenia. Previous studies have reported that the protein and mRNA levels of the synapsin 2 (SYN2) and complexin 2 (CPLX2) genes were decreased in patients with schizophrenia. Synapsin 2 and complexin 2 are involved in synaptogenesis and the modulation of neurotransmitter release. This report presents a study of the association of polymorphisms of SYN2 and CPLX2 with schizophrenia in the Korean population. METHODS: Six single nucleotide polymorphisms (SNPs) and one 5-bp insertion/deletion in SYN2 and five SNPs in CPLX2 were genotyped in 154 Korean patients with schizophrenia and 133 control patients using direct sequencing or restriction fragment length polymorphism analysis. An intermarker linkage disequilibrium map was constructed for each gene. RESULTS: Although there was no significant difference in the genotypic distributions and allelic frequencies of either SYN2 or CPLX2 polymorphisms between the schizophrenia and control groups, the two-way haplotype analyses revealed significant associations with the disease (P < 0.05 after Bonferroni correction). The three-way haplotype analyses also revealed a significant association of SYN2 with schizophrenia (P < 0.001 after Bonferroni correction). CONCLUSION: These results suggest that both SYN2 and CPLX2 may confer susceptibility to schizophrenia in the Korean population.

SUBMITTER: Lee HJ

PROVIDER: S-EPMC1215472 | biostudies-literature | 2005 Aug

REPOSITORIES: biostudies-literature

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Association study of polymorphisms in synaptic vesicle-associated genes, SYN2 and CPLX2, with schizophrenia.

Lee Hee Jae HJ Song Ji Young JY Kim Jong Woo JW Jin Sheng-Yu SY Hong Mi Suk MS Park Jin Kyoung JK Chung Joo-Ho JH Shibata Hiroki H Fukumaki Yasuyuki Y

Behavioral and brain functions : BBF 20050831

<h4>Background</h4>The occurrence of aberrant functional connectivity in the neuronal circuit is one of the integrative theories of the etiology of schizophrenia. Previous studies have reported that the protein and mRNA levels of the synapsin 2 (SYN2) and complexin 2 (CPLX2) genes were decreased in patients with schizophrenia. Synapsin 2 and complexin 2 are involved in synaptogenesis and the modulation of neurotransmitter release. This report presents a study of the association of polymorphisms ...[more]

PMID: 16131404

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Project description:BACKGROUND: The expression of ?-opioid receptor has important role in cognitive dysfunction in Schizophrenia (SZ). The results of studies about the association of polymorphisms of ?-opioid receptor gene (OPRM1) with SZ were inconsistent. METHODS: We conducted a case-control study to investigate the genetic association between OPRM1 polymorphisms and SZ among the Han chinese population. 264 SZ patients and 264 age-matched control subjects were recruited. Four SNPs of OPRM1 were successfully genotyped by using PCR-RFLP. RESULTS: Of four polymorphisms, rs1799971 and rs2075572 were shown to associate with SZ. Compared with the A allele of rs1799971 and C allele of rs2075572, the G allele of rs1799971 and rs2075572 was associated with an almost 0.46-fold risk (OR=0.46, 95% CI: 0.357-0.59, P<0.01) and 0.7-fold risk (OR=0.707, 95% CI: 0.534-0.937, P=0.015) of the occurrence of SZ,. When subjects were divided by gender, rs1799971 remained significant difference only in males (OR=0.309, 95% CI: 0.218-0.439 for G allele, P<0.01), and rs2075572 only in females (OR=0.399, 95% CI: 0.246-0.648 for G allele, P<0.01). In secondary analysis with subsets of patients, the G allele of rs1799971 (compared to the A allele) was associated with a decreased risk of all patients and male patients with apathy symptoms (OR=0.086, 95% CI: 0.048-0.151, P=0.01; OR=0.083, 95% CI: 0.045-0.153, P<0.01), and the G allele of rs2075572 (compared to the C allele) was associated with a decreased risk of all patients and female patients with positive family history (OR=0.468, 95% CI: 0.309-0.71, P<0.01; OR=0.34, 95% CI: 0.195-0.593, P<0.01). In addition, haplotype analysis revealed that two SNP haplotypes (A-C-C-G and G-C-C-A) were associated with decreased risks of SZ (P<0.01). The other two (G-C-C-G and G-G-C-G) with increased risks of SZ (P<0.01). CONCLUSIONS: The present study demonstrated for the first time that the OPRM1 polymorphism may be a risk factor for schizophrenia in the Han Chinese. Further studies are needed to give a global view of this polymorphism in pathogenesis of schizophrenia in a large-scale sample, family-based association design or well-defined subgroups of schizophrenia.

Project description:IntroductionSchizophrenia is a chronic heterogenic neurodevelopment disorder. Many genes interfere in the development of SCZ. All four genes, NrCAM, PRODH, ANK3, and ANKK1, which were evaluated in this study, were previously reported to be associated with Schizophrenia. The NrCAM contributes to creating cognitive deficiencies through the CAM's signaling pathway. PRODH plays a vital role in creating SCZ negative symptoms through the signaling pathway of glutamatergic and NMDA receptors. ANK3 affects ion channel and molecular adhesion in Ranvier and initial segments of axons, leading to mental retardation, sleep disorder, and SCZ. ANKK1 encodes a protein kinase and was reported to be associated with alcohol addiction, Attention Deficit Hyperactivity Disorder (ADHD), and SCZ.MethodsThe subjects were selected from Schizophrenic patients referring to the Psychiatric Ward of Imam-Hussein Hospital and Schizophrenic Patients Support Institution (AHEBBA). 95 (30 Schizoaffective patients, 57 Paranoid patients, and 8 disorganized) patients were recruited as the subjects in the present case-control association study. 120 healthy subjects were recruited from the Tehran Medical Genetics Laboratory staff and a group of students from the Islamic Azad University of Science and Research in Tehran. The genotypes were determined with molecular genotyping techniques of PCR-RFLP, ARMS-PCR, and Cycle sequencing. Results were analyzed by the Chi-Square test using SPSS V. 24 and R, SNP STATE Package to investigate significant differences between cases and controls.ResultsThe incidence of schizophrenia was 68% and 32% among men and women, respectively. The evaluation of the allelic association between schizophrenia and all the candidate SNPs showed a significant association between NrCAM's SNP rs10235968 and SCZ (P=0.001). Haplotype T, T, C in rs10235968, rs6967368, rs3763463, respectively, within the NrCAM gene, showed significant association with schizophrenia disorder (P=0.0001).ConclusionNo association was found between other candidate SNPs and SCZ among the subjects.

Dataset Information

Association study of polymorphisms in synaptic vesicle-associated genes, SYN2 and CPLX2, with schizophrenia.

Publications

Association study of polymorphisms in synaptic vesicle-associated genes, SYN2 and CPLX2, with schizophrenia.

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