Polymorphisms in MicroRNA Genes And Genes Involving in NMDAR Signaling and Schizophrenia: A Case-Control Study in Chinese Han Population

Yanxia Zhang; Mei Fan; Qingzhong Wang; Guang He; Yingmei Fu; Huafang Li; Shunying Yu

doi:10.1038/srep12984

journal article Open Access Aug 10, 2015

Polymorphisms in MicroRNA Genes And Genes Involving in NMDAR Signaling and Schizophrenia: A Case-Control Study in Chinese Han Population

Yanxia Zhang

Mei Fan Qingzhong Wang

Guang He

Yingmei Fu Huafang Li

Shunying Yu

Scientific Reports Vol. 5 No. 1 · Springer Science and Business Media LLC

View at Publisher Save 10.1038/srep12984

Abstract

AbstractDisturbances in glutamate signaling caused by disruption of N-methyl-D-aspartate-type glutamate receptor (NMDAR) have been implicated in schizophrenia. Findings suggested that miR-219, miR-132 and miR-107 could involve in NMDAR signaling by influencing the expression of pathway genes or the signaling transmission and single nucleotide polymorphisms (SNPs) within miRNA genes or miRNA target sites could result in their functional changes. Therefore, we hypothesized that SNPs in miRNAs and/or their target sites were associated with schizophrenia. 3 SNPs inhsa-pri-miR-219/132/107and 6 SNPs in 3′UTRs ofGRIN2A/2B/3AandCAMK2Gwere selected and genotyped in a case-control study of 1041 schizophrenia cases and 953 healthy controls in Chinese Han population. In the present study,GRIN2Brs890 showed significant associations with schizophrenia. Further functional analyses showed that the rs890 variant C allele led to significantly lower luciferase activity, compared with the A allele. MDR analysis showed that a 4-locus model including rs107822, rs2306327, rs890 and rs12342026 was the best model. These findings suggest thatGRIN2Bmay be associated with schizophrenia and interaction effects of the polymorphisms inhsa-miR-219,CAKM2G,GRIN2BandGRIN3Amay confer susceptibility to schizophrenia in the Chinese Han population.

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References

34

[1]

Picchioni, M. M. & Murray, R. M. Schizophrenia. BMJ 335, 91–95 (2007). 10.1136/bmj.39227.616447.be

[2]

Hunsberger, J. G., Austin, D. R., Chen, G. & Manji, H. K. MicroRNAs in mental health: from biological underpinnings to potential therapies. Neuromolecular Med 11, 173–182 (2009). 10.1007/s12017-009-8070-5

[3]

Forero, D. A., van der Ven, K., Callaerts, P. & Del-Favero, J. miRNA genes and the brain: implications for psychiatric disorders. Hum Mutat 31, 1195–1204 (2010). 10.1002/humu.21344

[4]

MicroRNAs

David P Bartel

Cell 2004 10.1016/s0092-8674(04)00045-5

[5]

Zhu, Y., Kalbfleisch, T., Brennan, M. D. & Li, Y. A MicroRNA gene is hosted in an intron of a schizophrenia-susceptibility gene. Schizophr Res 109, 86–89 (2009). 10.1016/j.schres.2009.01.022

[6]

Miller, B. H. & Wahlestedt, C. MicroRNA dysregulation in psychiatric disease. Brain Res 1338, 89–99 (2010). 10.1016/j.brainres.2010.03.035

[7]

Kantrowitz, J. T. & Javitt, D. C. N-methyl-d-aspartate (NMDA) receptor dysfunction or dysregulation: the final common pathway on the road to schizophrenia? Brain Res Bull 83, 108–121 (2010). 10.1016/j.brainresbull.2010.04.006

[8]

Kocerha, J. et al. MicroRNA-219 modulates NMDA receptor-mediated neurobehavioral dysfunction. Proc Natl Acad Sci USA 106, 3507–3512 (2009). 10.1073/pnas.0805854106

[9]

microRNA Modulation of Circadian-Clock Period and Entrainment

Hai-Ying M. Cheng, Joseph W. Papp, Olga Varlamova et al.

Neuron 2007 10.1016/j.neuron.2007.05.017

[10]

Beveridge, N. J., Tooney, P. A., Carroll, A. P., Tran, N. & Cairns, M. J. Down-regulation of miR-17 family expression in response to retinoic acid induced neuronal differentiation. Cell Signal 21, 1837–1845 (2009). 10.1016/j.cellsig.2009.07.019

[11]

Nudelman, A. S. et al. Neuronal activity rapidly induces transcription of the CREB-regulated microRNA-132, in vivo. Hippocampus 20, 492–498 (2010). 10.1002/hipo.20646

[12]

Miller, B. H. et al. MicroRNA-132 dysregulation in schizophrenia has implications for both neurodevelopment and adult brain function. Proc Natl Acad Sci USA 109, 3125–3130 (2012). 10.1073/pnas.1113793109

[13]

Kim, A. H. et al. MicroRNA expression profiling in the prefrontal cortex of individuals affected with schizophrenia and bipolar disorders. Schizophr Res 124, 183–191 (2010). 10.1016/j.schres.2010.07.002

[14]

Beveridge, N. J., Gardiner, E., Carroll, A. P., Tooney, P. A. & Cairns, M. J. Schizophrenia is associated with an increase in cortical microRNA biogenesis. Mol Psychiatry 15, 1176–1189 (2010). 10.1038/mp.2009.84

[15]

Mishra, P. J. & Bertino, J. R. MicroRNA polymorphisms: the future of pharmacogenomics, molecular epidemiology and individualized medicine. Pharmacogenomics 10, 399–416 (2009). 10.2217/14622416.10.3.399

[16]

Shi, Y. Y. & He, L. SHEsis, a powerful software platform for analyses of linkage disequilibrium, haplotype construction and genetic association at polymorphism loci. Cell Res 15, 97–98 (2005). 10.1038/sj.cr.7290286

[17]

Moore, J. H. Computational analysis of gene-gene interactions using multifactor dimensionality reduction. Expert Rev Mol Diagn 4, 795–803 (2004). 10.1586/14737159.4.6.795

[18]

Hahn, L. W., Ritchie, M. D. & Moore, J. H. Multifactor dimensionality reduction software for detecting gene-gene and gene-environment interactions. Bioinformatics 19, 376–382 (2003). 10.1093/bioinformatics/btf869

[19]

Ritchie, M. D., Hahn, L. W. & Moore, J. H. Power of multifactor dimensionality reduction for detecting gene-gene interactions in the presence of genotyping error, missing data, phenocopy and genetic heterogeneity. Genet Epidemiol 24, 150–157 (2003). 10.1002/gepi.10218

[20]

Moore, J. H. & White, B. C. Tuning ReliefF for genome-wide genetic analysis. Lect Notes Comput Sc 4447, 166–175 (2007). 10.1007/978-3-540-71783-6_16

[21]

Noble, W. S. How does multiple testing correction work? Nat Biotechnol 27, 1135–1137 (2009). 10.1038/nbt1209-1135

[22]

Han, J. et al. Molecular basis for the recognition of primary microRNAs by the Drosha-DGCR8 complex. Cell 125, 887–901 (2006). 10.1016/j.cell.2006.03.043

[23]

Diederichs, S. & Haber, D. A. Sequence variations of microRNAs in human cancer: alterations in predicted secondary structure do not affect processing. Cancer Res 66, 6097–6104 (2006). 10.1158/0008-5472.can-06-0537

[24]

Wu, M. et al. Genetic variations of microRNAs in human cancer and their effects on the expression of miRNAs. Carcinogenesis 29, 1710–1716 (2008). 10.1093/carcin/bgn073

[25]

Calin, G. A. et al. A MicroRNA signature associated with prognosis and progression in chronic lymphocytic leukemia. N Engl J Med 353, 1793–1801 (2005). 10.1056/nejmoa050995

[26]

Pullmann, R. Jr. et al. Differential stability of thymidylate synthase 3′-untranslated region polymorphic variants regulated by AUF1. J Biol Chem 281, 23456–23463 (2006). 10.1074/jbc.m600282200

[27]

Allen, N. C. et al. Systematic meta-analyses and field synopsis of genetic association studies in schizophrenia: the SzGene database. Nat Genet 40, 827–834 (2008). 10.1038/ng.171

[28]

Demontis, D. et al. Association of GRIN1 and GRIN2A-D with schizophrenia and genetic interaction with maternal herpes simplex virus-2 infection affecting disease risk. Am J Med Genet B Neuropsychiatr Genet 156B, 913–922 (2011). 10.1002/ajmg.b.31234

[29]

Di Maria, E. et al. Variations in the NMDA receptor subunit 2B gene (GRIN2B) and schizophrenia: a case-control study. Am J Med Genet B Neuropsychiatr Genet 128B, 27–29 (2004). 10.1002/ajmg.b.30028

[30]

Ohtsuki, T. et al. Mutation analysis of the NMDAR2B (GRIN2B) gene in schizophrenia. Mol Psychiatry 6, 211–216 (2001). 10.1038/sj.mp.4000808

[31]

Paoletti, P. & Neyton, J. NMDA receptor subunits: function and pharmacology. Curr Opin Pharmacol 7, 39–47 (2007). 10.1016/j.coph.2006.08.011

[32]

Mueller, H. T. & Meador-Woodruff, J. H. NR3A NMDA receptor subunit mRNA expression in schizophrenia, depression and bipolar disorder. Schizophr Res 71, 361–370 (2004). 10.1016/j.schres.2004.02.016

[33]

Gulli, R. et al. A putative regulatory subunit (NR3A) of the NMDA receptor complex as candidate gene for susceptibility to schizophrenia: a case-control study. Psychiatr Genet 17, 355–356 (2007). 10.1097/ypg.0b013e328133f74f

[34]

Shen, Y. C. et al. Exomic sequencing of the ionotropic glutamate receptor N-methyl-D-aspartate 3A gene (GRIN3A) reveals no association with schizophrenia. Schizophr Res 114, 25–32 (2009). 10.1016/j.schres.2009.07.005

Cited By

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Schizophrenia Genetics

A. E. Gareeva, E. K. Khusnutdinova · 2018

Russian Journal of Genetics

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References

Details

Published: Aug 10, 2015
Vol/Issue: 5(1)
License: View

Authors

College of Intelligence Science and Technology, National University of Defense Technology, Changsha, China

Cite This Article

Yanxia Zhang, Mei Fan, Qingzhong Wang, et al. (2015). Polymorphisms in MicroRNA Genes And Genes Involving in NMDAR Signaling and Schizophrenia: A Case-Control Study in Chinese Han Population. Scientific Reports, 5(1). https://doi.org/10.1038/srep12984

Polymorphisms in MicroRNA Genes And Genes Involving in NMDAR Signaling and Schizophrenia: A Case-Control Study in Chinese Han Population

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