Korean Journal of Biological Psychiatry (생물정신의학)

The Korean Society of Biological Psychiatry (대한생물정신의학회)
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Association Analysis of Neuregulin 3 Gene with Schizophrenia in a Korean Population

한국인에서 Neuregulin 3(NRG3) 유전자와 조현병의 연합 연구

  • Shin, Su-Jin (Department of Psychiatry, College of Medicine, Soonchunhyang University, Soonchunhyang University Hospital) ;
  • Choi, Jong-Taek (Department of Psychiatry, College of Medicine, Soonchunhyang University, Soonchunhyang University Hospital) ;
  • Kim, Ji-Won (Department of Psychiatry, College of Medicine, Soonchunhyang University, Soonchunhyang University Hospital) ;
  • Roh, Yang-Ho (Department of Psychiatry, College of Medicine, Soonchunhyang University, Soonchunhyang University Hospital) ;
  • Park, Byung-Lae (Department of Genetic Epidemiology, SNP Genetics, Inc.) ;
  • Bae, Joon-Seol (Department of Life Science, Sogang University) ;
  • Shin, Hyoung-Doo (Department of Life Science, Sogang University) ;
  • Choi, Ihn-Geun (Department of Neuropsychiatry, Hallym University College of Medicine, Hangang Sacred Heart Hospital) ;
  • Han, Sang-Woo (Department of Psychiatry, College of Medicine, Soonchunhyang University, Soonchunhyang University Hospital) ;
  • Hwang, Jae-Uk (Department of Psychiatry, College of Medicine, Soonchunhyang University, Soonchunhyang University Hospital) ;
  • Woo, Sung-Il (Department of Psychiatry, College of Medicine, Soonchunhyang University, Soonchunhyang University Hospital)
  • 신수진 (순천향대학교 의과대학 순천향대학교병원 정신건강의학교실) ;
  • 최종택 (순천향대학교 의과대학 순천향대학교병원 정신건강의학교실) ;
  • 김지원 (순천향대학교 의과대학 순천향대학교병원 정신건강의학교실) ;
  • 노양호 (순천향대학교 의과대학 순천향대학교병원 정신건강의학교실) ;
  • 박병래 ((주)에스엔피 제네틱스) ;
  • 배준설 (2서강대학교 생명공학과) ;
  • 신형두 (2서강대학교 생명공학과) ;
  • 최인근 (한림대학교 의과대학 한강성심병원 정신건강의학교실) ;
  • 한상우 (순천향대학교 의과대학 순천향대학교병원 정신건강의학교실) ;
  • 황재욱 (순천향대학교 의과대학 순천향대학교병원 정신건강의학교실) ;
  • 우성일 (순천향대학교 의과대학 순천향대학교병원 정신건강의학교실)
  • Received : 2012.05.23
  • Accepted : 2012.07.06
  • Published : 2012.08.31
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Abstract

Objectives : Located on chromosome 10q22-q23, the human neuregulin 3 (NRG3) is suggested as a strong positional and functional candidate gene involved in the pathogenesis of schizophrenia. Several case-control studies examining the association between polymorphisms on NRG3 gene with schizophrenia and/or its traits (such as delusion) have been reported recently in cohorts of Han Chinese, Ashkenazi Jews, Australians, white Americans of Western European ancestry and Koreans. Thus, this study aimed to investigate the association of one SNP in exon 9 (rs2295933) of NRG3 gene with the risk of schizophrenia in a Korean population. Methods : Using TaqMan assay, rs2295933 in the exon 9 of NRG3 was genotyped in 435 patients with schizophrenia as cases and 393 unrelated healthy individuals as controls. Differences in frequency distributions were analyzed using logistic regression models following various modes of genetic inheritance and controlling for age and sex as covariates. Results : Subsequent analysis revealed that the frequency distribution of rs2295933 of NRG3 was not different between schizophrenia patients and healthy controls of Korean ethnicity. Conclusions : This study does not support the role of NRG3 in schizophrenia in a Korean population.

Keywords

References

  1. Cardno AG, Gottesman II. Twin studies of schizophrenia: from bow-and-arrow concordances to star wars Mx and functional genomics. Am J Med Genet 2000;97:12-17. https://doi.org/10.1002/(SICI)1096-8628(200021)97:1<12::AID-AJMG3>3.0.CO;2-U
  2. Stefansson H, Sigurdsson E, Steinthorsdottir V, Bjornsdottir S, Sigmundsson T, Ghosh S, et al. Neuregulin 1 and susceptibility to schizophrenia. Am J Hum Genet 2002;71:877-892. https://doi.org/10.1086/342734
  3. Stefansson H, Sarginson J, Kong A, Yates P, Steinthorsdottir V, Gudfinnsson E, et al. Association of neuregulin 1 with schizophrenia confirmed in a Scottish population. Am J Hum Genet 2003;72:83-87. https://doi.org/10.1086/345442
  4. Fukui N, Muratake T, Kaneko N, Amagane H, Someya T. Supportive evidence for neuregulin 1 as a susceptibility gene for schizophrenia in a Japanese population. Neurosci Lett 2006;396:117-120. https://doi.org/10.1016/j.neulet.2005.11.015
  5. Yang JZ, Si TM, Ruan Y, Ling YS, Han YH, Wang XL, et al. Association study of neuregulin 1 gene with schizophrenia. Mol Psychiatry 2003;8:706-709. https://doi.org/10.1038/sj.mp.4001377
  6. Kim JH, Park BL, Pasaje CF, Bae JS, Park CS, Cha B, et al. Lack of associations of neuregulin 1 variations with schizophrenia and smooth pursuit eye movement abnormality in a Korean population. J Mol Neurosci 2012;46:476-482. https://doi.org/10.1007/s12031-011-9619-y
  7. Straub RE, Jiang Y, MacLean CJ, Ma Y, Webb BT, Myakishev MV, et al. Genetic variation in the 6p22.3 gene DTNBP1, the human ortholog of the mouse dysbindin gene, is associated with schizophrenia. Am J Hum Genet 2002;71:337-348. https://doi.org/10.1086/341750
  8. Schwab SG, Knapp M, Mondabon S, Hallmayer J, Borrmann-Hassenbach M, Albus M, et al. Support for association of schizophrenia with genetic variation in the 6p22.3 gene, dysbindin, in sib-pair families with linkage and in an additional sample of triad families. Am J Hum Genet 2003;72:185-190. https://doi.org/10.1086/345463
  9. Van Den Bogaert A, Schumacher J, Schulze TG, Otte AC, Ohlraun S, Kovalenko S, et al. The DTNBP1 (dysbindin) gene contributes to schizophrenia, depending on family history of the disease. Am J Hum Genet 2003;73:1438-1443. https://doi.org/10.1086/379928
  10. Kirov G, Ivanov D, Williams NM, Preece A, Nikolov I, Milev R, et al. Strong evidence for association between the dystrobrevin binding protein 1 gene (DTNBP1) and schizophrenia in 488 parent-offspring trios from Bulgaria. Biol Psychiatry 2004;55:971-975. https://doi.org/10.1016/j.biopsych.2004.01.025
  11. Funke B, Finn CT, Plocik AM, Lake S, DeRosse P, Kane JM, et al. Association of the DTNBP1 locus with schizophrenia in a U.S. population. Am J Hum Genet 2004;75:891-898. https://doi.org/10.1086/425279
  12. Tang JX, Zhou J, Fan JB, Li XW, Shi YY, Gu NF, et al. Family-based association study of DTNBP1 in 6p22.3 and schizophrenia. Mol Psychiatry 2003;8:717-718. https://doi.org/10.1038/sj.mp.4001287
  13. Numakawa T, Yagasaki Y, Ishimoto T, Okada T, Suzuki T, Iwata N, et al. Evidence of novel neuronal functions of dysbindin, a susceptibility gene for schizophrenia. Hum Mol Genet 2004;13:2699-2708. https://doi.org/10.1093/hmg/ddh280
  14. Moon HI, Lee YJ, Park BL, Shin HD, Choi IG, Han SH, et al. Association analysis of polymorphisms on Dystrobrevin Binding Protein 1 (DTNBP1) Gene with schizophrenia in the Korean population. Korean J Biol Psychiatry 2009;16:149-158.
  15. Devon RS, Anderson S, Teague PW, Burgess P, Kipari TM, Semple CA, et al. Identification of polymorphisms within Disrupted in Schizophrenia 1 and Disrupted in Schizophrenia 2, and an investigation of their association with schizophrenia and bipolar affective disorder. Psychiatr Genet 2001;11:71-78. https://doi.org/10.1097/00041444-200106000-00003
  16. Hodgkinson CA, Goldman D, Jaeger J, Persaud S, Kane JM, Lipsky RH, et al. Disrupted in schizophrenia 1 (DISC1): association with schizophrenia, schizoaffective disorder, and bipolar disorder. Am J Hum Genet 2004;75:862-872. https://doi.org/10.1086/425586
  17. Sachs NA, Sawa A, Holmes SE, Ross CA, DeLisi LE, Margolis RL. A frameshift mutation in Disrupted in Schizophrenia 1 in an American family with schizophrenia and schizoaffective disorder. Mol Psychiatry 2005;10:758-764. https://doi.org/10.1038/sj.mp.4001667
  18. Zhang F, Sarginson J, Crombie C, Walker N, St Clair D, Shaw D. Genetic association between schizophrenia and the DISC1 gene in the Scottish population. Am J Med Genet B Neuropsychiatr Genet 2006;141B:155-159. https://doi.org/10.1002/ajmg.b.30274
  19. Zhang X, Tochigi M, Ohashi J, Maeda K, Kato T, Okazaki Y, et al. Association study of the DISC1/TRAX locus with schizophrenia in a Japanese population. Schizophr Res 2005;79:175-180. https://doi.org/10.1016/j.schres.2005.05.023
  20. Mei L, Xiong WC. Neuregulin 1 in neural development, synaptic plasticity and schizophrenia. Nat Rev Neurosci 2008;9:437-452. https://doi.org/10.1038/nrn2392
  21. Faraone SV, Hwu HG, Liu CM, Chen WJ, Tsuang MM, Liu SK, et al. Genome scan of Han Chinese schizophrenia families from Taiwan: confirmation of linkage to 10q22.3. Am J Psychiatry 2006;163:1760-1766. https://doi.org/10.1176/appi.ajp.163.10.1760
  22. Fallin MD, Lasseter VK, Wolyniec PS, McGrath JA, Nestadt G, Valle D, et al. Genomewide linkage scan for schizophrenia susceptibility loci among Ashkenazi Jewish families shows evidence of linkage on chromosome 10q22. Am J Hum Genet 2003;73:601-611. https://doi.org/10.1086/378158
  23. Wang YC, Chen JY, Chen ML, Chen CH, Lai IC, Chen TT, et al. Neuregulin 3 genetic variations and susceptibility to schizophrenia in a Chinese population. Biol Psychiatry 2008;64:1093-1096. https://doi.org/10.1016/j.biopsych.2008.07.012
  24. Chen PL, Avramopoulos D, Lasseter VK, McGrath JA, Fallin MD, Liang KY, et al. Fine mapping on chromosome 10q22-q23 implicates Neuregulin 3 in schizophrenia. Am J Hum Genet 2009;84:21-34. https://doi.org/10.1016/j.ajhg.2008.12.005
  25. Morar B, Dragovic M, Waters FA, Chandler D, Kalaydjieva L, Jablensky A. Neuregulin 3 (NRG3) as a susceptibility gene in a schizophrenia subtype with florid delusions and relatively spared cognition. Mol Psychiatry 2011;16:860-866. https://doi.org/10.1038/mp.2010.70
  26. Kao WT, Wang Y, Kleinman JE, Lipska BK, Hyde TM, Weinberger DR, et al. Common genetic variation in Neuregulin 3 (NRG3) influences risk for schizophrenia and impacts NRG3 expression in human brain. Proc Natl Acad Sci U S A 2010;107:15619-15624. https://doi.org/10.1073/pnas.1005410107
  27. Pasaje CF, Bae JS, Park BL, Cheong HS, Kim JH, Park TJ, et al. Neuregulin 3 does not confer risk for schizophrenia and smooth pursuit eye movement abnormality in a Korean population. Genes Brain Behav 2011;10:828-833. https://doi.org/10.1111/j.1601-183X.2011.00722.x
  28. Huang YZ, Won S, Ali DW, Wang Q, Tanowitz M, Du QS, et al. Regulation of neuregulin signaling by PSD-95 interacting with ErbB4 at CNS synapses. Neuron 2000;26:443-455. https://doi.org/10.1016/S0896-6273(00)81176-9
  29. Kwon OB, Longart M, Vullhorst D, Hoffman DA, Buonanno A. Neuregulin-1 reverses long-term potentiation at CA1 hippocampal synapses. J Neurosci 2005;25:9378-9383. https://doi.org/10.1523/JNEUROSCI.2100-05.2005
  30. Banerjee A, Macdonald ML, Borgmann-Winter KE, Hahn CG. Neuregulin 1-erbB4 pathway in schizophrenia: from genes to an interactome. Brain Res Bull 2010;83:132-139. https://doi.org/10.1016/j.brainresbull.2010.04.011
  31. Sauna ZE, Kimchi-Sarfaty C. Understanding the contribution of synonymous mutations to human disease. Nat Rev Genet 2011;12:683-691.
  32. Plotkin JB, Kudla G. Synonymous but not the same: the causes and consequences of codon bias. Nat Rev Genet 2011;12:32-42. https://doi.org/10.1038/nrg2899
  33. Czech A, Fedyunin I, Zhang G, Ignatova Z. Silent mutations in sight: co-variations in tRNA abundance as a key to unravel consequences of silent mutations. Mol Biosyst 2010;6:1767-1772. https://doi.org/10.1039/c004796c