Skip to main content
Log in

The Interaction of TXNIP and AFq1 Genes Increases the Susceptibility of Schizophrenia

  • Published:
Molecular Neurobiology Aims and scope Submit manuscript

Abstract

Although previous studies showed the reduced risk of cancer in patients with schizophrenia, whether patients with schizophrenia possess genetic factors that also contribute to tumor suppressor is still unknown. In the present study, based on our previous microarray data, we focused on the tumor suppressor genes TXNIP and AF1q, which differentially expressed in patients with schizophrenia. A total of 413 patients and 578 healthy controls were recruited. We found no significant differences in genotype, allele, or haplotype frequencies at the selected five single nucleotide polymorphisms (SNPs) (rs2236566 and rs7211 in TXNIP gene; rs10749659, rs2140709, and rs3738481 in AF1q gene) between patients with schizophrenia and controls. However, we found the association between the interaction of TXNIP and AF1q with schizophrenia by using the MDR method followed by traditional statistical analysis. The best gene-gene interaction model identified was a three-locus model TXNIP (rs2236566, rs7211)-AF1q (rs2140709). After traditional statistical analysis, we found the high-risk genotype combination was rs2236566 (GG)-rs7211(CC)-rs2140709(CC) (OR = 1.35 [1.03–1.76]). The low-risk genotype combination was rs2236566 (GT)-rs7211(CC)-rs2140709(CC) (OR = 0.67 [0.49–0.91]). Our finding suggested statistically significant role of interaction of TXNIP and AF1q polymorphisms (TXNIP-rs2236566, TXNIP-rs7211, and AF1q-rs2769605) in schizophrenia susceptibility.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Chen Y, Bang S, McMullen MF, Kazi H, Talbot K, Ho MX, et al (2016) Neuronal activity-induced sterol regulatory element binding protein-1 (SREBP1) is disrupted in dysbindin-null mice-potential link to cognitive impairment in schizophrenia. Mol Neurobiol

  2. Fakhoury M (2016) Role of the endocannabinoid system in the pathophysiology of schizophrenia. Mol Neurobiol

  3. Jablensky A, Lawrence D (2001) Schizophrenia and cancer: is there a need to invoke a protective gene? Arch Gen Psychiatry 58:579–580

    Article  CAS  PubMed  Google Scholar 

  4. Cohen M, Dembling B, Schorling J (2002) The association between schizophrenia and cancer: a population-based mortality study. Schizophr Res 57:139–146

    Article  PubMed  Google Scholar 

  5. Park JK, Lee HJ, Kim JW et al (2004) Differences in p53 gene polymorphisms between Korean schizophrenia and lung cancer patients. Schizophr Res 67:71–74

    Article  CAS  PubMed  Google Scholar 

  6. Yang Y, Xiao Z, Chen W et al (2004) Tumor suppressor gene TP53 is genetically associated with schizophrenia in the Chinese population. Neurosci Lett 369:126–131

    Article  CAS  PubMed  Google Scholar 

  7. Catts VS, Catts SV (2000) Apoptosis and schizophrenia: is the tumour suppressor gene, p53, a candidate susceptibility gene? Schizophr Res 41:405–415

    Article  CAS  PubMed  Google Scholar 

  8. Cui D, Yao H, Wang X, Zhu B, JIang K (2004) Microarray analysis of altered gene expression in schizophrenia. Chin J Psychiatry 37:4–8

    Google Scholar 

  9. Brzustowicz LM, Hodgkinson KA, Chow EW, Honer WG, Bassett AS (2000) Location of a major susceptibility locus for familial schizophrenia on chromosome 1q21-q22. Science 288:678–682

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Brzustowicz LM, Simone J, Mohseni P et al (2004) Linkage disequilibrium mapping of schizophrenia susceptibility to the CAPON region of chromosome 1q22. Am J Hum Genet 74:1057–1063

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Brzustowicz LM, Hayter JE, Hodgkinson KA, Chow EW, Bassett AS (2002) Fine mapping of the schizophrenia susceptibility locus on chromosome 1q22. Hum Hered 54:199–209

    Article  CAS  PubMed  Google Scholar 

  12. Nishinaka Y, Masutani H, Oka S et al (2004) Importin alpha1 (Rch1) mediates nuclear translocation of thioredoxin-binding protein-2/vitamin D (3)-up-regulated protein 1. J Biol Chem 279:37559–37565

    Article  CAS  PubMed  Google Scholar 

  13. Takagi Y, Tokime T, Nozaki K, Gon Y, Kikuchi H, Yodoi J (1998) Redox control of neuronal damage during brain ischemia after middle cerebral artery occlusion in the rat: immunohistochemical and hybridization studies of thioredoxin. J Cereb Blood Flow Metab 18:206–214

    Article  CAS  PubMed  Google Scholar 

  14. Lovell MA, Xie C, Gabbita SP, Markesbery WR (2000) Decreased thioredoxin and increased thioredoxin reductase levels in Alzheimer’s disease brain. Free Radic Biol Med 28:418–427

    Article  CAS  PubMed  Google Scholar 

  15. Lin HJ, Shaffera KM, Sun Z et al (2004) AF1q, a differentially expressed gene during neuronal differentiation, transforms HEK cells into neuron-like cells. Mol Brain Res 131:126–130

    Article  CAS  PubMed  Google Scholar 

  16. Lin Z, Su Y, Zhang C et al (2013) The interaction of BDNF and NTRK2 gene increases the susceptibility of paranoid schizophrenia. PLoS One 8(9), e74264

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Burmeister M, McInnis MG, Zollner S (2008) Psychiatric genetics: progress amid controversy. Nat Rev Genet 9:527–540

    Article  CAS  PubMed  Google Scholar 

  18. Li Z, Zhang Y, Wang Z et al (2013) The role of BDNF, NTRK2 gene and their interaction in development of treatment-resistant depression: data from multicenter, prospective, longitudinal clinic practice. J Psychiatr Res 47:8–14

    Article  PubMed  Google Scholar 

  19. Shi YY, He L (2005) SHEsis, a powerful software platform for analyses of linkage disequilibrium, haplotype construction, and genetic association at polymorphism loci. Cell Res 15:97–98

    Article  CAS  PubMed  Google Scholar 

  20. Gauderman WJ, Morrison JM (2006) QUANTO 1.1: a computer program for power and sample size calculations for genetic-epidemiology studies

  21. Ritchie MD, Hahn LW, Roodi N et al (2001) Multifactor-dimensionality reduction reveals high-order interactions among estrogen-metabolism genes in sporadic breast cancer. Am J Hum Genet 69:138–147

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Dervieux T, Wessels JA, Kremer JM et al (2012) Patterns of interaction between genetic and nongenetic attributes and methotrexate efficacy in rheumatoid arthritis. Pharmacogenet Genomics 22:1–9

    Article  CAS  PubMed  Google Scholar 

  23. Lillberg K et al (2003) Stressful life events and risk of breast cancer in 10,808 women: a cohort study. Am J Epidemiol 157:415–423

    Article  PubMed  Google Scholar 

  24. Buccheri G (1998) Depressive reactions to lung cancer are common and often followed by a poor outcome. Eur Respir J 11:173–178

    Article  CAS  PubMed  Google Scholar 

  25. Chida Y, Hamer M, Wardle J, Steptoe A (2008) Do stress-related psychosocial factors contribute to cancer incidence and survival? Nat Clin Pract Oncol 5:466–475

    Article  PubMed  Google Scholar 

  26. Thaker PH et al (2006) Chronic stress promotes tumor growth and angiogenesis in a mouse model of ovarian carcinoma. Nat Med 12:939–944

    Article  CAS  PubMed  Google Scholar 

  27. Feng Z, Liu L, Zhang C et al (2012) Chronic restraint stress attenuates p53 function and promotes tumorigenesis. Proc Natl Acad Sci U S A 109:7013–7018

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Vousden KH, Prives C (2009) Blinded by the light: the growing complexity of p53. Cell 137:413–431

    Article  CAS  PubMed  Google Scholar 

  29. Lieberman JA (1999) Is schizophrenia a neurodegenerative disorder? A clinical and neurobiological perspective. Biol Psychiatry 46:729–739

    Article  CAS  PubMed  Google Scholar 

  30. Margolis RL, Chuang DM, Post RM (1994) Programmed cell death: implications for neuropsychiatric disorders. Biol Psychiatry 35:946–956

    Article  CAS  PubMed  Google Scholar 

  31. Berger GE, Wood S, McGorry PD (2003) Incipient neurovulnerability and neuroprotection in early psychosis. Psychopharmacol Bull 37:e79–e101

    Google Scholar 

  32. Jarskog LF, Selinger ES, Lieberman JA, Gilmore JH (2004) Apoptotic proteins in the temporal cortex in schizophrenia: high Bax/Bcl-2 ratio without caspase-3 activation. Am J Psychiatry 161:109–115

    Article  PubMed  Google Scholar 

  33. Jarskog LF, Glantz LA, Gilmore JH, Lieberman JA (2005) Apoptotic mechanisms in the pathophysiology of schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry 29:846–858

    Article  CAS  PubMed  Google Scholar 

  34. Cui DH, Jiang KD, Jiang SD, Xu YF, Yao H (2005) The tumor suppressor Adenomatous Polyposis Coli gene is associated with susceptibility to schizophrenia. Mol Psychiatry 10:669–677

    Article  CAS  PubMed  Google Scholar 

  35. Onouchi T, Kobayashi K, Sakai K et al (2014) Targeted deletion of the C-terminus of the mouse adenomatous polyposis coli tumor suppressor results in neurologic phenotypes related to schizophrenia. Mol Brain 7:21

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

The authors are very grateful to all participants. We thank Drs. Liwei Liao, Zheng Chen, and Ying Qiao for help with sample collection.

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Zezhi Li or Donghong Cui.

Ethics declarations

All procedures were reviewed and approved by Institutional Review Boards of Shanghai Mental Health Center.

Funding and Disclosures

This study was supported by the National Natural Science Foundation of China (81401127, 81171266, 81271481), Shanghai Natural Science Foundation (13ZR1460500), Shanghai Municipal Commission of health and Family Planning Found (Zezhi Li), and Shanghai Key Laboratory of Psychotic Disorders (13dz2260500,14-K06). All funding for this study had no further role in study design, data analysis, and in the decision to submit the paper for publication. The authors declare no conflict of interest.

Additional information

Yousong Su and Wenhua Ding contributed equally to the work.

Electronic Supplementary Material

Below is the link to the electronic supplementary material.

Supplementary Table 1

(DOC 27 kb)

Supplementary Table 2

(DOC 28 kb)

Supplementary Table 3

(DOC 31 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Su, Y., Ding, W., Xing, M. et al. The Interaction of TXNIP and AFq1 Genes Increases the Susceptibility of Schizophrenia. Mol Neurobiol 54, 4806–4812 (2017). https://doi.org/10.1007/s12035-016-9954-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12035-016-9954-7

Keywords

Navigation