Association between regulating synaptic membrane exocytosis 2 gene polymorphisms and degenerative lumbar scoliosis

Kim,Ki‑Tack; Lee,Jong Seok; Lee,Byoung Wook; Seok,Hosik; Jeon,Hye Sook; Kim,Jun Ho; Chung,Joo‑Ho

doi:10.3892/br.2013.101

Association between regulating synaptic membrane exocytosis 2 gene polymorphisms and degenerative lumbar scoliosis

Authors:
- Ki‑Tack Kim
- Jong Seok Lee
- Byoung Wook Lee
- Hosik Seok
- Hye Sook Jeon
- Jun Ho Kim
- Joo‑Ho Chung
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Affiliations: Department of Orthopedic Surgery, Spine Center, Kyung Hee University East‑West Neo Medical Center, Kangdong‑gu, Seoul 134‑090, Republic of Korea, Department of Emergency Medicine, Kyung Hee University, Dongdaemun‑gu, Seoul 130‑701, Republic of Korea, Department of Biochemistry and Molecular Biology, Kyung Hee University, Dongdaemun‑gu, Seoul 130‑701, Republic of Korea, Kohwang Medical Research Institute, School of Medicine, Kyung Hee University, Dongdaemun‑gu, Seoul 130‑701, Republic of Korea
Published online on: May 9, 2013 https://doi.org/10.3892/br.2013.101
Pages: 619-623

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Abstract

Degenerative lumbar scoliosis (DLS) is a spinal deformity that develops after skeletal maturity and progresses with age. In contrast to adolescent idiopathic scoliosis, the genetic association of DLS has not yet been elucidated. The purpose of this study was to investigate the association between regulating synaptic membrane exocytosis 2 (RIMS2, OBOE) gene polymorphisms and DLS. Two coding single‑nucleotide polymorphisms [rs2028945 (Gln1200Gln) and rs10461 (Ala1327Ala)] of RIMS2 were selected and genotyped by direct sequencing. As a result, the rs10461 was associated with DLS in allele frequencies (P=0.008) and genotype distributions (P=0.006 in the codominant model, 0.018 in the dominant model and 0.029 in the recessive model). In the analysis of haplotypes, two haplotypes exhibited significant differences between the control and DLS groups (CC haplotype, P=0.009 in the codominant model, 0.038 in the dominant model and 0.030 in the recessive model; CT haplotype, P=0.041 in the codominant model and 0.021 in the dominant model). These findings suggest that RIMS2 may be associated with the development of DLS.

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1.	Aebi M: The adult scoliosis. Eur Spine J. 14:925–948. 2005. View Article : Google Scholar
2.	Ploumis A, Transfledt EE and Denis F: Degenerative lumbar scoliosis associated with spinal stenosis. Spine J. 7:428–436. 2007. View Article : Google Scholar
3.	Oskouian RJ Jr and Shaffrey CI: Degenerative lumbar scoliosis. Neurosurg Clin N Am. 17:299–315. 2006. View Article : Google Scholar
4.	Ferrari S, Rizzoli R and Bonjour JP: Heritable and nutritional influences on bone mineral mass. Aging (Milano). 10:205–213. 1998.PubMed/NCBI
5.	Kawaguchi Y, Kanamori M, Ishihara H, Ohmori K, Matsui H and Kimura T: The association of lumbar disc disease with vitamin-D receptor gene polymorphism. J Bone Joint Surg Am. 84-A:2022–2028. 2002.PubMed/NCBI
6.	Dresbach T, Qualmann B, Kessels MM, Garner CC and Gundelfinger ED: The presynaptic cytomatrix of brain synapses. Cell Mol Life Sci. 58:94–116. 2001. View Article : Google Scholar : PubMed/NCBI
7.	Lonart G: RIM1: an edge for presynaptic plasticity. Trends Neurosci. 25:329–332. 2002. View Article : Google Scholar : PubMed/NCBI
8.	Schoch S, Mittelstaedt T, Kaeser PS, et al: Redundant functions of RIM1α and RIM2α in Ca²⁺-triggered neurotransmitter release. EMBO J. 25:5852–5863. 2006.
9.	Ohtsuka T, Takao-Rikitsu E, Inoue E, et al: Cast: a novel protein of the cytomatrix at the active zone of synapses that forms a ternary complex with RIM1 and munc13-1. J Cell Biol. 158:577–590. 2002. View Article : Google Scholar : PubMed/NCBI
10.	Wang Y, Liu X, Biederer T and Südhof TC: A family of RIM-binding proteins regulated by alternative splicing: implications for the genesis of synaptic active zones. Proc Natl Acad Sci USA. 99:14464–14469. 2002. View Article : Google Scholar : PubMed/NCBI
11.	Wang Y, Sugita S and Südhof TC: The RIM/NIM family of neuronal C₂domain proteins. Interactions with Rab3 and a new class of Src homology 3 domain proteins. J Biol Chem. 275:20033–20044. 2000.PubMed/NCBI
12.	Coppola T, Magnin-Luthi S, Perret-Menoud V, et al: Direct interaction of the Rab3 effector RIM with Ca²⁺channels, SNAP-25, and synaptotagmin. J Biol Chem. 276:32756–32762. 2001. View Article : Google Scholar : PubMed/NCBI
13.	Schoch S, Castillo PE, Jo T, et al: RIM1alpha forms a protein scaffold for regulating neurotransmitter release at the active zone. Nature. 415:321–326. 2002. View Article : Google Scholar : PubMed/NCBI
14.	Schoch S and Gundelfinger ED: Molecular organization of the presynaptic active zone. Cell Tissue Res. 326:379–391. 2006. View Article : Google Scholar : PubMed/NCBI
15.	Wang Y and Südhof TC: Genomic definition of RIM proteins: evolutionary amplification of a family of synaptic regulatory proteins. Genomics. 81:126–137. 2003. View Article : Google Scholar : PubMed/NCBI
16.	Pritchett JW and Bortel DT: Degenerative symptomatic lumbar scoliosis. Spine (Phila Pa 1976). 18:700–703. 1993. View Article : Google Scholar : PubMed/NCBI
17.	Chin KR, Furey C and Bohlman HH: Risk of progression in de novo low-magnitude degenerative lumbar curves: natural history and literature review. Am J Orthop (Belle Mead NJ). 38:404–409. 2009.PubMed/NCBI
18.	Solé X, Guinó E, Valls J, Iniesta R and Moreno V: SNPStats: a web tool for the analysis of association studies. Bioinformatics. 22:1928–1929. 2006.
19.	Gabriel SB, Schaffner SF, Nguyen H, et al: The structure of haplotype blocks in the human genome. Science. 296:2225–2229. 2002. 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 : PubMed/NCBI
21.	Betz A, Thakur P, Junge HJ, et al: Functional interaction of the active zone proteins Munc13-1 and RIM1 in synaptic vesicle priming. Neuron. 30:183–196. 2001. View Article : Google Scholar : PubMed/NCBI
22.	Wang X, Hu B, Zimmermann B and Kilimann MW: Rim1 and rabphilin-3 bind Rab3-GTP by composite determinants partially related through N-terminal alpha-helix motifs. J Biol Chem. 276:32480–32488. 2001. View Article : Google Scholar : PubMed/NCBI
23.	Zhen M and Jin Y: The liprin protein SYD-2 regulates the differentiation of presynaptic termini in C. elegans. Nature. 401:371–375. 1999. View Article : Google Scholar : PubMed/NCBI
24.	Kaufmann N, DeProto J, Ranjan R, et al: Drosophila liprin-alpha and the receptor phosphatase Dlar control synapse morphogenesis. Neuron. 34:27–38. 2002. View Article : Google Scholar
25.	Koushika SP, Richmond JE, Hadwiger G, et al: A post-docking role for active zone protein Rim. Nat Neurosci. 4:997–1005. 2001. View Article : Google Scholar : PubMed/NCBI
26.	Castillo PE, Schoch S, Schmitz F, et al: RIM1alpha is required for presynaptic long-term potentiation. Nature. 415:327–330. 2002. View Article : Google Scholar : PubMed/NCBI
27.	Weidenhofer J, Bowden NA, Scott RJ and Tooney PA: Altered gene expression in the amygdala in schizophrenia: up-regulation of genes located in the cytomatrix active zone. Mol Cell Neurosci. 31:243–250. 2006. View Article : Google Scholar : PubMed/NCBI
28.	Weidenhofer J, Scott RJ and Tooney PA: Investigation of the expression of genes affecting cytomatrix active zone function in the amygdala in schizophrenia: effects of antipsychotic drugs. J Psychiatr Res. 43:282–290. 2009. View Article : Google Scholar : PubMed/NCBI
29.	Takao-Rikitsu E, Mochida S, Inoue E, et al: Physical and functional interaction of the active zone proteins, CAST, RIM1, and Bassoon, in neurotransmitter release. J Cell Biol. 164:301–311. 2004. View Article : Google Scholar : PubMed/NCBI