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Common Polymorphisms Within QPCT Gene Are Associated with the Susceptibility of Schizophrenia in a Han Chinese Population

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Abstract

A recent genome-wide association study conducted in Caucasians has identified glutaminyl-peptide cyclotransferase (QPCT) gene as a susceptibility gene for schizophrenia, as its common single nucleotide polymorphism (SNP) rs2373000 was significantly associated with the risk of this disease. To date, this finding has not been validated in other populations or ethnic groups. The aim of this study was to investigate the association of common SNPs spanning QPCT gene with the susceptibility of schizophrenia in a Han Chinese population comprising 440 schizophrenia patients and 450 control subjects. A total of 6 tagSNPs including rs2373000 was selected and then genotyped in our sample. Although the relation between rs2373000 and the risk of schizophrenia was not successfully replicated, we showed for the first time that the minor allele (C) of rs3770752 was associated with a reduced risk of schizophrenia (odds ratio (OR) = 0.645; 95 % confidence interval (CI) 0.486–0.855; P corrected = 0.012) in our cohorts. Meanwhile, this allele seemed to modify the schizophrenia risk through a dominant manner (CC + CT vs. TT, OR = 0.625; 95 % CI 0.457–0.854; P corrected = 0.03). In addition, we found that the minor allele (T) of rs3770748 remarkably reduced the schizophrenia risk via a recessive manner (TT vs. TC + CC, OR = 0.618; 95 % CI: 0.449–0.851; P corrected = 0.03). Taken together, these findings demonstrate a significant association between common SNPs within QPCT gene and schizophrenia risk in a Han Chinese population, suggesting QPCT gene may represent a susceptibility gene for this disease.

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References

  1. Perala J, Suvisaari J, Saarni SI, Kuoppasalmi K, Isometsa E, Pirkola S, Partonen T, Tuulio-Henriksson A et al (2007) Lifetime prevalence of psychotic and bipolar I disorders in a general population. Arch Gen Psychiatry 64(1):19–28. doi:10.1001/archpsyc.64.1.19

    Article  PubMed  Google Scholar 

  2. Prince M, Patel V, Saxena S, Maj M, Maselko J, Phillips MR, Rahman A (2007) No health without mental health. Lancet 370(9590):859–877. doi:10.1016/S0140-6736(07)61238-0

    Article  PubMed  Google Scholar 

  3. Allan CL, Cardno AG, McGuffin P (2008) Schizophrenia: from genes to phenes to disease. Curr Psychiatry Rep 10(4):339–343

    Article  PubMed  Google Scholar 

  4. Ivleva E, Thaker G, Tamminga CA (2008) Comparing genes and phenomenology in the major psychoses: schizophrenia and bipolar 1 disorder. Schizophr Bull 34(4):734–742. doi:10.1093/schbul/sbn051

    Article  PubMed  PubMed Central  Google Scholar 

  5. Havik B, Le Hellard S, Rietschel M, Lybaek H, Djurovic S, Mattheisen M, Muhleisen TW, Degenhardt F et al (2011) The complement control-related genes CSMD1 and CSMD2 associate to schizophrenia. Biol Psychiatry 70(1):35–42. doi:10.1016/j.biopsych.2011.01.030

    Article  CAS  PubMed  Google Scholar 

  6. Yue WH, Wang HF, Sun LD, Tang FL, Liu ZH, Zhang HX, Li WQ, Zhang YL et al (2011) Genome-wide association study identifies a susceptibility locus for schizophrenia in Han Chinese at 11p11.2. Nat Genet 43(12):1228–1231. doi:10.1038/ng.979

    Article  CAS  PubMed  Google Scholar 

  7. Hamshere ML, Walters JT, Smith R, Richards AL, Green E, Grozeva D, Jones I, Forty L et al (2013) Genome-wide significant associations in schizophrenia to ITIH3/4, CACNA1C and SDCCAG8, and extensive replication of associations reported by the Schizophrenia PGC. Mol Psychiatry 18(6):708–712. doi:10.1038/mp.2012.67

    Article  CAS  PubMed  Google Scholar 

  8. Ripke S, O’Dushlaine C, Chambert K, Moran JL, Kahler AK, Akterin S, Bergen SE, Collins AL et al (2013) Genome-wide association analysis identifies 13 new risk loci for schizophrenia. Nat Genet 45(10):1150–1159. doi:10.1038/ng.2742

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Alexandru A, Jagla W, Graubner S, Becker A, Bauscher C, Kohlmann S, Sedlmeier R, Raber KA et al (2011) Selective hippocampal neurodegeneration in transgenic mice expressing small amounts of truncated Abeta is induced by pyroglutamate-Abeta formation. J Neurosci 31(36):12790–12801. doi:10.1523/JNEUROSCI.1794-11.2011

    Article  CAS  PubMed  Google Scholar 

  10. Schilling S, Hoffmann T, Rosche F, Manhart S, Wasternack C, Demuth HU (2002) Heterologous expression and characterization of human glutaminyl cyclase: evidence for a disulfide bond with importance for catalytic activity. Biochemistry 41(35):10849–10857

    Article  CAS  PubMed  Google Scholar 

  11. LaCrosse AL, Olive MF (2013) Neuropeptide systems and schizophrenia. CNS Neurol Disord Drug Targets 12(5):619–632

    Article  CAS  PubMed  Google Scholar 

  12. Li Z, Boules M, Williams K, Gordillo A, Li S, Richelson E (2010) Similarities in the behavior and molecular deficits in the frontal cortex between the neurotensin receptor subtype 1 knockout mice and chronic phencyclidine-treated mice: relevance to schizophrenia. Neurobiol Dis 40(2):467–477. doi:10.1016/j.nbd.2010.07.011

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Sharma RP, Martis B, Rosen C, Jonalagadda J, Nemeroff CB, Bissette G (2001) CSF thyrotropin-releasing hormone concentrations differ in patients with schizoaffective disorder from patients with schizophrenia or mood disorders. J Psychiatr Res 35(5):287–291

    Article  CAS  PubMed  Google Scholar 

  14. Brambilla F, Aguglia E, Massironi R, Maggioni M, Grillo W, Castiglioni R, Catalano M, Drago F (1986) Neuropeptide therapies in chronic schizophrenia: TRH and vasopressin administration. Neuropsychobiology 15(3–4):114–121, 118253

    CAS  PubMed  Google Scholar 

  15. Walton NM, de Koning A, Xie X, Shin R, Chen Q, Miyake S, Tajinda K, Gross AK, Kogan JH, Heusner CL, Tamura K, Matsumoto M (2014) Gastrin-releasing peptide contributes to the regulation of adult hippocampal neurogenesis and neuronal development. Stem Cells. doi:10.1002/stem.1740.

  16. Meller CA, Henriques JA, Schwartsmann G, Roesler R (2004) The bombesin/gastrin releasing peptide receptor antagonist RC-3095 blocks apomorphine but not MK-801-induced stereotypy in mice. Peptides 25(4):585–588. doi:10.1016/j.peptides.2004.01.003

    Article  CAS  PubMed  Google Scholar 

  17. Gu LZ, Jiang T, Cheng ZH, Zhang YC, Ou MM, Chen MC, Zhou ZH, Ling WM (2014) rs11098403 polymorphism near NDST3 is associated with a reduced risk of schizophrenia in a Han Chinese population. Neurosci Lett 581:42–45. doi:10.1016/j.neulet.2014.08.018

    Article  CAS  PubMed  Google Scholar 

  18. Gu LZ, Jiang T, Cheng ZH, Zhang YC, Ou MM, Chen MC, Ling WM (2015) TSNARE1 polymorphisms are associated with schizophrenia susceptibility in Han Chinese. J Neural Transm 122(6):929–932. doi:10.1007/s00702-014-1348-2

    Article  CAS  PubMed  Google Scholar 

  19. Jiang T, Yu JT, Tan MS, Wang HF, Wang YL, Zhu XC, Zhang W, Tan L (2014) Genetic variation in PICALM and Alzheimer’s disease risk in Han Chinese. Neurobiol Aging 35(4):934 e931–933. doi:10.1016/j.neurobiolaging.2013.09.014

    Article  Google Scholar 

  20. Jiang T, Yu JT, Wang YL, Wang HF, Zhang W, Hu N, Tan L, Sun L, Tan MS, Zhu XC (2014) The genetic variation of ARRB2 is associated with late-onset Alzheimer’s disease in Han Chinese. Curr Alzheimer Res 11(4):408–412

    Article  CAS  PubMed  Google Scholar 

  21. Wang J, Yu JT, Jiang T, Tan MS, Wang HF, Tan L, Hu N, Sun L et al (2014) Association of LRRTM3 polymorphisms with late-onset Alzheimer’s disease in Han Chinese. Exp Gerontol 52:18–22. doi:10.1016/j.exger.2014.01.013

    Article  PubMed  Google Scholar 

  22. Tan MS, Yu JT, Jiang T, Zhu XC, Guan HS, Tan L (2014) Genetic variation in BIN1 gene and Alzheimer’s disease risk in Han Chinese individuals. Neurobiol Aging 35(7):e1781–1788. doi:10.1016/j.neurobiolaging.2014.01.151

    Article  Google Scholar 

  23. Tan MS, Yu JT, Jiang T, Zhu XC, Wang HF, Zhang W, Wang YL, Jiang W et al (2013) NLRP3 polymorphisms are associated with late-onset Alzheimer’s disease in Han Chinese. J Neuroimmunol 265(1–2):91–95. doi:10.1016/j.jneuroim.2013.10.002

    Article  CAS  PubMed  Google Scholar 

  24. Yu JT, Jiang T, Wang YL, Wang HF, Zhang W, Hu N, Tan L, Sun L et al (2014) Triggering receptor expressed on myeloid cells 2 variant is rare in late-onset Alzheimer’s disease in Han Chinese individuals. Neurobiol Aging 35(4):937 e931–933. doi:10.1016/j.neurobiolaging.2013.10.075

    Google Scholar 

  25. Zhu XC, Tan L, Jiang T, Tan MS, Zhang W, Yu JT (2014) Association of IL-12A and IL-12B polymorphisms with Alzheimer’s disease susceptibility in a Han Chinese population. J Neuroimmunol. doi:10.1016/j.jneuroim.2014.06.026

    PubMed Central  Google Scholar 

  26. Capon F, Allen MH, Ameen M, Burden AD, Tillman D, Barker JN, Trembath RC (2004) A synonymous SNP of the corneodesmosin gene leads to increased mRNA stability and demonstrates association with psoriasis across diverse ethnic groups. Hum Mol Genet 13(20):2361–2368. doi:10.1093/hmg/ddh273

    Article  CAS  PubMed  Google Scholar 

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Corresponding authors

Correspondence to Teng Jiang, Jun-Shan Zhou or Ying-Dong Zhang.

Ethics declarations

This work was supported by the National Natural Science Foundation of China to T.J. (81501092), the Natural Science Foundation of Jiangsu Province to T.J. (BK20150091) and Y.D.Z. (BK20151084), and the China Postdoctoral Science Foundation to T.J. (2015 M580448).

Conflict of Interest

The authors declare that they have no competing interests.

Additional information

Qiao-Quan Zhang and Teng Jiang should be regarded as co-first authors.

Electronic Supplementary Material

Below is the link to the electronic supplementary material.

ESM 1

Supplementary Table S1. General information of tSNPs within QPCT in our samples. (DOC 44 kb)

ESM 2

Supplementary Table S2. Comparison of genotypes and allele frequencies of tSNPs within QPCT between control subjects from the exploratory and replication samples and those obtained from the HapMap database. (DOC 53 kb)

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Zhang, QQ., Jiang, T., Gu, LZ. et al. Common Polymorphisms Within QPCT Gene Are Associated with the Susceptibility of Schizophrenia in a Han Chinese Population. Mol Neurobiol 53, 6362–6366 (2016). https://doi.org/10.1007/s12035-015-9541-3

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  • DOI: https://doi.org/10.1007/s12035-015-9541-3

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