Investigating the potential genetic association between RANBP9 polymorphisms and the risk of schizophrenia

Bae,Joon   Seol; Kim,Jason   Yongha; Park,Byung‑Lae; Cheong,Hyun   Sub; Kim,Jeong‑Hyun; Namgoong,Suhg; Kim,Ji‑On; Park,Chul   Soo; Kim,Bong‑Jo; Lee,Cheol‑Soon; Lee,Migyung; Choi,Woo   Hyuk; Shin,Tae‑Min; Hwang,Jaeuk; Shin,Hyoung   Doo; Woo,Sung‑Il

doi:10.3892/mmr.2014.3045

Investigating the potential genetic association between RANBP9 polymorphisms and the risk of schizophrenia

Authors:
- Joon Seol Bae
- Jason Yongha Kim
- Byung‑Lae Park
- Hyun Sub Cheong
- Jeong‑Hyun Kim
- Suhg Namgoong
- Ji‑On Kim
- Chul Soo Park
- Bong‑Jo Kim
- Cheol‑Soon Lee
- Migyung Lee
- Woo Hyuk Choi
- Tae‑Min Shin
- Jaeuk Hwang
- Hyoung Doo Shin
- Sung‑Il Woo
View Affiliations

Affiliations: Laboratory of Translational Genomics, Samsung Genome Institute, Samsung Medical Center, Seoul 135‑710, Republic of Korea, Laboratory of Genomic Diversity, Department of Life Science, Sogang University, Seoul 121‑742, Republic of Korea, Department of Genetic Epidemiology, SNP Genetics, Inc., Sogang University, Seoul 121‑742, Republic of Korea, Department of Psychiatry, College of Medicine, Gyeongsang National University, Jinju, Gyeongsang Nam Do, 660‑751, Republic of Korea, Department of General Psychiatry, Seoul National Hospital, Seoul 110‑799, Republic of Korea, Department of Biomedical Engineering, Yonsei University, Wonju, Gangwon 220‑710, Republic of Korea, Department of Neuropsychiatry, Soonchunhyang University Hospital, Seoul 420‑767, Republic of Korea
Published online on: December 4, 2014 https://doi.org/10.3892/mmr.2014.3045
Pages: 2975-2980

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Schizophrenia is a serious mental disorder that is affected by genetic and environmental factors. As the disease has a high heritability rate, genetic studies identifying candidate genes for schizophrenia have been conducted in various populations. The gene for human Ran‑binding protein 9 (RANBP9) is a newly discovered candidate gene for schizophrenia. As RANBP9 is a small guanosine‑5'‑triphosphate‑binding protein that interacts with the disrupted in schizophrenia 1 protein, it is considered to be an important molecule in the pathogenesis of schizophrenia. However, to date, no study has examined the possible association between the genetic variations of RANBP9 and the risk of schizophrenia. In the present study, it was hypothesized that RANBP9 variations may influence the risk of schizophrenia. In order to investigate the association between RANBP9 polymorphisms and the risk of schizophrenia and smooth pursuit eye movement (SPEM) abnormalities, a case‑control association analysis was performed. Using a TaqMan assay, five single‑nucleotide polymorphisms and an insertion/deletion variation within the start codon region of RANBP9 were genotyped. Five major haplotypes were identified in 449 patients with schizophrenia and 393 unrelated healthy individuals as controls (total, n=842). However, the association analyses revealed no associations between all genetic variants and schizophrenia and SPEM abnormality. To the best of our knowledge, this is the first study to investigate an association between RANBP9 polymorphisms and schizophrenia and SPEM abnormality. The findings of allele frequencies and association results in this study may aid in further genetic etiological studies in schizophrenia in various populations.

View Figures

View References

1	McGrath J, Saha S, Chant D and Welham J: Schizophrenia: a concise overview of incidence, prevalence, and mortality. Epidemiol Rev. 30:67–76. 2008. View Article : Google Scholar : PubMed/NCBI
2	Torrey EF: Prevalence studies in schizophrenia. Br J Psychiatry. 150:598–608. 1987. View Article : Google Scholar : PubMed/NCBI
3	Park HJ, Westin CF, Kubicki M, et al: White matter hemisphere asymmetries in healthy subjects and in schizophrenia: a diffusion tensor MRI study. Neuroimage. 23:213–223. 2004. View Article : Google Scholar : PubMed/NCBI
4	Hof PR, Haroutunian V, Friedrich VL Jr, et al: Loss and altered spatial distribution of oligodendrocytes in the superior frontal gyrus in schizophrenia. Biol Psychiatry. 53:1075–1085. 2003. View Article : Google Scholar : PubMed/NCBI
5	Hulshoff Pol HE, Schnack HG, Mandl RC, et al: Focal white matter density changes in schizophrenia: reduced inter-hemispheric connectivity. Neuroimage. 21:27–35. 2004. View Article : Google Scholar : PubMed/NCBI
6	Kubicki M, McCarley RW and Shenton ME: Evidence for white matter abnormalities in schizophrenia. Curr Opin Psychiatry. 18:121–134. 2005. View Article : Google Scholar
7	Uranova N, Orlovskaya D, Vikhreva O, et al: Electron microscopy of oligodendroglia in severe mental illness. Brain Res Bull. 55:597–610. 2001. View Article : Google Scholar : PubMed/NCBI
8	Uranova NA, Vostrikov VM, Orlovskaya DD and Rachmanova VI: Oligodendroglial density in the prefrontal cortex in schizophrenia and mood disorders: a study from the Stanley Neuropathology Consortium. Schizophr Res. 67:269–275. 2004. View Article : Google Scholar : PubMed/NCBI
9	Mitterauer B: The incoherence hypothesis of schizophrenia: based on decomposed oligodendrocyte-axonic relations. Med Hypotheses. 69:1299–1304. 2007. View Article : Google Scholar : PubMed/NCBI
10	Murrin LC and Talbot JN: RanBPM, a scaffolding protein in the immune and nervous systems. J Neuroimmune Pharmacol. 2:290–295. 2007. View Article : Google Scholar : PubMed/NCBI
11	Nakayama AY, Harms MB and Luo L: Small GTPases Rac and Rho in the maintenance of dendritic spines and branches in hippocampal pyramidal neurons. J Neurosci. 20:5329–5338. 2000.PubMed/NCBI
12	Rex EB, Rankin ML, Ariano MA and Sibley DR: Ethanol regulation of D(1) dopamine receptor signaling is mediated by protein kinase C in an isozyme-specific manner. Neuropsychopharmacology. 33:2900–2911. 2008. View Article : Google Scholar : PubMed/NCBI
13	Kutay U, Hartmann E, Treichel N, et al: Identification of two novel RanGTP-binding proteins belonging to the importin beta superfamily. J Biol Chem. 275:40163–40168. 2000. View Article : Google Scholar : PubMed/NCBI
14	Blackwood DH, Fordyce A, Walker MT, St Clair DM, Porteous DJ and Muir WJ: Schizophrenia and affective disorders--cosegregation with a translocation at chromosome 1q42 that directly disrupts brain-expressed genes: clinical and P300 findings in a family. Am J Hum Genet. 69:428–433. 2001. View Article : Google Scholar : PubMed/NCBI
15	Millar JK, Christie S, Anderson S, et al: Genomic structure and localisation within a linkage hotspot of Disrupted In Schizophrenia 1, a gene disrupted by a translocation segregating with schizophrenia. Mol Psychiatry. 6:173–178. 2001. View Article : Google Scholar : PubMed/NCBI
16	Rex EB, Rankin ML, Yang Y, et al: Identification of RanBP 9/10 as interacting partners for protein kinase C (PKC) gamma/delta and the D1 dopamine receptor: regulation of PKC-mediated receptor phosphorylation. Mol Pharmacol. 78:69–80. 2010. View Article : Google Scholar : PubMed/NCBI
17	American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4th edition. American Psychiatric Association; Washington, D.C., WA: 1994
18	Park BL, Shin HD, Cheong HS, et al: Association analysis of COMT polymorphisms with schizophrenia and smooth pursuit eye movement abnormality. J Hum Genet. 54:709–712. 2009. View Article : Google Scholar : PubMed/NCBI
19	Stephens M, Smith NJ and Donnelly P: A new statistical method for haplotype reconstruction from population data. Am J Hum Genet. 68:978–989. 2001. View Article : Google Scholar : PubMed/NCBI
20	Barrett JC, Fry B, Maller J and Daly MJ: Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics. 21:263–265. 2005. View Article : Google Scholar
21	Wang D, Li Z, Messing EM and Wu G: Activation of Ras/Erk pathway by a novel MET-interacting protein RanBPM. J Biol Chem. 277:36216–36222. 2002. View Article : Google Scholar : PubMed/NCBI
22	Lakshmana MK, Hayes CD, Bennett SP, et al: Role of RanBP9 on amyloidogenic processing of APP and synaptic protein levels in the mouse brain. FASEB J. 26:2072–2083. 2012. View Article : Google Scholar : PubMed/NCBI
23	Morris S, Leung J, Sharp C, Blackwood D, Muir W and St Clair D: Screening schizophrenic patients for mutations in the amyloid precursor protein gene. Psychiatr Genet. 4:23–27. 1994. View Article : Google Scholar : PubMed/NCBI
24	Albertini V, Benussi L, Paterlini A, et al: Distinct cerebrospinal fluid amyloid-beta peptide signatures in cognitive decline associated with Alzheimer’s disease and schizophrenia. Electrophoresis. 33:3738–3744. 2012. View Article : Google Scholar : PubMed/NCBI
25	McLean SL, Idris NF, Woolley ML and Neill JC: D(1)-like receptor activation improves PCP-induced cognitive deficits in animal models: Implications for mechanisms of improved cognitive function in schizophrenia. Eur Neuropsychopharmacol. 19:440–450. 2009. View Article : Google Scholar : PubMed/NCBI
26	Menon RP, Gibson TJ and Pastore A: The C terminus of fragile X mental retardation protein interacts with the multi-domain Ran-binding protein in the microtubule-organising centre. J Mol Biol. 343:43–53. 2004. View Article : Google Scholar : PubMed/NCBI
27	Cheong HS, Park BL, Kim EM, et al: Association of RANBP1 haplotype with smooth pursuit eye movement abnormality. Am J Med Genet B Neuropsychiatr Genet. 156B:67–71. 2011. View Article : Google Scholar
28	Kehlenbach RH, Dickmanns A, Kehlenbach A, Guan T and Gerace L: A role for RanBP1 in the release of CRM1 from the nuclear pore complex in a terminal step of nuclear export. J Cell Biol. 145:645–657. 1999. View Article : Google Scholar : PubMed/NCBI