Skip to main content
SpringerLink
Log in

Association analysis of genetic variant of rs13331 in PSD95 gene with autism spectrum disorders: A case-control study in a Chinese population

  • Published:
Journal of Huazhong University of Science and Technology [Medical Sciences] Aims and scope Submit manuscript

Summary

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by high heritability. Recently, autism, the most profound form of ASD, has been increasingly attributed to synaptic abnormalities. Postsynaptic density 95 (PSD95), encoding PSD protein-95, was found essential for synaptic formation, maturation and plasticity at a PSD of excitatory synapse. It is possibly a crucial candidate gene for the pathogenesis of ASD. To identify the relationship between the rs13331 of PSD95 gene and ASD, we performed a case-control study in 212 patients and 636 controls in a Chinese population by using a polymerase chain reaction-restriction fragment length polymerase (PCR-RFLP) assay. The results showed that in genetic analysis of the heterozygous model, an association between the T allele of the rs13331 and ASD was found in the dominant model (OR=1.709, 95% CI 1.227–2.382, P=0.002) and the additive model (OR=1.409, 95% CI=1.104–1.800, P=0.006). Our data indicate that the genetic mutation C>T at the rs13331 in the PSD95 gene is strikingly associated with an increased risk of ASD.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Sandin S, Lichtenstein P, Kuja-Halkola R, et al. The familial risk of autism. JAMA, 2014,311(17):1770–1777

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Elsabbagh M, Divan G, Koh YJ, et al. Global prevalence of autism and other pervasive developmental disorders. Autism Res, 2012,5(3):160–179

    Article  PubMed  PubMed Central  Google Scholar 

  3. Rumsey JM, Rapoport JL, Sceery WR. Autistic children as adults: psychiatric, social, and behavioral outcomes. J AmAcad Child Psychiatry, 1985,24(4):465–473

    Article  CAS  Google Scholar 

  4. Kao YC, Kramer JM, Liljenquist K, et al. Association between impairment, function, and daily life task management in children and adolescents with autism. Dev Med Child Neurol, 2015,57(1):68–74

    Article  PubMed  PubMed Central  Google Scholar 

  5. Visser EM, Berger HJ, Van Schrojenstein LVH, et al. Cognitive shifting and externalising problem behaviour in intellectual disability and autism spectrum disorder. J Intellect Disabil Res, 2015,59(8):755–766

    Article  CAS  PubMed  Google Scholar 

  6. Baron-Cohen S. Social and pragmatic deficits in autism: cognitive or affective? J Autism Dev Disord, 1988,18(3): 379–402

    Article  CAS  PubMed  Google Scholar 

  7. Eicher JD, Gruen JR. Language impairment and dyslexia genes influence language skills in children with autism spectrum disorders. Autism Res, 2014,8(2):229–234

    Article  PubMed  PubMed Central  Google Scholar 

  8. Helt M, Kelley E, Kinsbourne M, et al. Can children with autism recover? If so, how? Neuropsychol Rev, 2008,18(4):339–366

    Article  PubMed  Google Scholar 

  9. Cohen S, Conduit R, Lockley SW, et al. The relationship between sleep and behavior in autism spectrum disorder (ASD): a review. J Neurodev Disord, 2014,6(1):44

    Article  PubMed  PubMed Central  Google Scholar 

  10. Ganz ML. The lifetime distribution of the incremental societal costs of autism. Arch Pediatr Adolesc Med, 2007,161(4):343–349

    Article  PubMed  Google Scholar 

  11. Ahmedani BK, Hock RM. Health care access and treatment for children with co-morbid autism and psychiatric conditions. Soc Psychiatry Psychiatr Epidemiol, 2012,47(11): 1807–1814

    Article  PubMed  Google Scholar 

  12. Montes G HJ. Child care problems and employment among families with preschool-aged children with autism in the United States. Pediatrics, 2008,122(1):202–208

    Article  Google Scholar 

  13. Nordenbaek C, Jorgensen M, Kyvik KO, et al. A Danish population-based twin study on autism spectrum disorders. Eur Child Adolesc Psychiatry, 2014,23(1):35–43

    Article  PubMed  Google Scholar 

  14. Folstein S, Rutter M. Genetic influences and infantile autism. Nature, 1977,265(5596):726–728

    Article  CAS  PubMed  Google Scholar 

  15. Rosenberg RE, Law JK, Yenokyan G, et al. Characteristics and concordance of autism spectrum disorders among 277 twin pairs. Arch PediatrAdolesc Med, 2009,163(10):907–914

    Article  Google Scholar 

  16. Lichtenstein P, Carlstrom E, Rastam M, et al. The genetics of autism spectrum disorders and related neuropsychiatric disorders in childhood. Am J Psychiatry, 2010,167(11): 1357–1363

    Article  PubMed  Google Scholar 

  17. Hallmayer J, Cleveland S, Torres A, et al. Genetic heritability and shared environmental factors among twin pairs with autism. Arch Gen Psychiatry, 2011,68(11):1095–1102

    Article  PubMed  PubMed Central  Google Scholar 

  18. Zoghbi HY. Postnatal neurodevelopmental disorders: meeting at the synapse? Science, 2003,302(5646):826–830

    Article  CAS  PubMed  Google Scholar 

  19. van Spronsen M, Hoogenraad CC. Synapse pathology in psychiatric and neurologic disease. Curr Neurol Neurosci Rep, 2010,10(3):207–214

    Article  PubMed  PubMed Central  Google Scholar 

  20. Gai X, Xie HM, Perin JC, et al. Rare structural variation of synapse and neurotransmission genes in autism. Mol Psychiatry, 2012,17(4):402–411

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Gylys KH, Fein JA, Yang F, et al. Synaptic changes in Alzheimer’s disease: increased amyloid-beta and gliosis in surviving terminals is accompanied by decreased PSD-95 fluorescence. Am J Pathol, 2004,165(5):1809–1817

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Aarts M, Liu Y, Liu L, et al. Treatment of ischemic brain damage by perturbing NMDA receptor-PSD-95 protein interactions. Science, 2002,298(5594):846–850

    Article  CAS  PubMed  Google Scholar 

  23. Cheng MC, Lu CL, Luu SU, et al. Genetic and functional analysis of the DLG4 gene encoding the post-synaptic density protein 95 in schizophrenia. PLoS One, 2010,5(12): e15107

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Chen J, Yu S, Fu Y, et al. Synaptic proteins and receptors defects in autism spectrum disorders. Front Cell Neurosci, 2014,8:276

    PubMed  PubMed Central  Google Scholar 

  25. Taft CE, Turrigiano GG. PSD-95 promotes the stabilization of young synaptic contacts. Philos Trans R SocLond B BiolSci, 2014,369(1633):20130134

    Article  Google Scholar 

  26. Migaud M, Charlesworth P, Dempster M, et al. Enhanced long-term potentiation and impaired learning in mice with mutant postsynaptic density-95 protein. Nature, 1998, 396(6710):433–439

    Article  CAS  PubMed  Google Scholar 

  27. Leuba G, Walzer C, Vernay A, et al. Postsynaptic density protein PSD-95 expression in Alzheimer’s disease and okadaic acid induced neuritic retraction. Neurobiol Dis, 2008,30(3):408–419

    Article  CAS  PubMed  Google Scholar 

  28. Chiocchetti AG, Kopp M, Waltes R, et al. Variants of the CNTNAP2 5' promoter as risk factors for autism spectrum disorders: a genetic and functional approach. Mol Psychiatry, 2014,20(7):839–849

    Article  PubMed  Google Scholar 

  29. Arking DE, Cutler DJ, Brune CW, et al. A common genetic variant in the neurexin superfamily member CNTNAP2 increases familial risk of autism. Am J Hum Genet, 2008,82(1):160–164

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Shao S, Xu S, Yang J, et al. A commonly carried genetic variant, rs9616915, in SHANK3 gene is associated with a reduced risk of autism spectrum disorder: replication in a Chinese population. MolBiol Rep, 2014,41(3):1591–1595

    CAS  Google Scholar 

  31. Chang SC, Pauls DL, Lange C, et al. Sex-specific association of a common variant of the XG gene with autism spectrum disorders. Am J Med Genet B Neuropsychiatr Genet, 2013,162B(7):742–750

    Article  PubMed  Google Scholar 

  32. Lord C, Cook EH, Leventhal BL, et al. Autism spectrum disorders. Neuron, 2000,28(2):355–363

    Article  CAS  PubMed  Google Scholar 

  33. Kennedy MB. Signal-processing machines at the postsynaptic density. Science, 2000,290(5492):750–754

    Article  CAS  PubMed  Google Scholar 

  34. Stephenson FA. Structure and trafficking of NMDA and GABAA receptors. BiochemSoc Trans, 2006,34(Pt 5):877–881

  35. Uchino S, Wada H, Honda S, et al. Direct interaction of post-synaptic density-95/Dlg/ZO-1 domaincontainingsynaptic molecule Shank3 with GluR1alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor. J Neurochem, 2006,97(4):1203–1214

    Article  CAS  PubMed  Google Scholar 

  36. Zheng S, Gray EE, Chawla G, et al. PSD-95 is post-transcriptionally repressed during early neural development by PTBP1 and PTBP2. Nat Neurosci, 2012,15(3): 381–388, S1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Chen L, Chetkovich DM, Petralia RS, et al. Stargazin regulates synaptic targeting of AMPA receptors by two distinct mechanisms. Nature, 2000,408(6815):936–943

    Article  CAS  PubMed  Google Scholar 

  38. Stathakis DG, Hoover KB, You Z, et al. Human postsynaptic density-95 (PSD95): location of the gene (DLG4) and possible function in nonneural as well as in neural tissues. Genomics, 1997,44(1):71–82

    Article  CAS  PubMed  Google Scholar 

  39. He Z, Shao S, Zhou J, et al. Does long time spending on the electronic devices affect the reading abilities? A cross-sectional study among Chinese school-aged children. Res Dev Disabil, 2014,35(12):3645–3654

    Article  PubMed  Google Scholar 

  40. Sun Z, Zou L, Zhang J, et al. Prevalence and associated risk factors of dyslexic children in a middle-sized city of China: a cross-sectional study. PLoS One, 2013,8(2): e56688

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Feyder M, Karlsson RM, Mathur P, et al. Association of mouse Dlg4 (PSD-95) gene deletion and human DLG4 gene variation with phenotypes relevant to autism spectrum disorders and Williams’ syndrome. Am J Psychiatry, 2010, 167(12):1508–1517

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Maternal and Child Health and MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China

    Jia Wang  (王 佳), Shan-shan Shao  (邵珊珊), Rui Kong  (孔 锐), Xiao-hui Zhang  (张晓慧), Jian-hua Gong  (龚建华) & Ran-ran Song  (宋然然)

  2. Maternity and Children Health Care Hospital of Luohu District, Shenzhen, 518019, China

    Li Li  (李 丽), Yan-lin Chen  (陈艳琳) & Jian-hua Gong  (龚建华)

  3. Central Hospital of Longhua New District, Shenzhen, 518000, China

    Zhen He  (何 珍)

Authors
  1. Jia Wang  (王 佳)
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Li Li  (李 丽)
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Shan-shan Shao  (邵珊珊)
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Zhen He  (何 珍)
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yan-lin Chen  (陈艳琳)
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Rui Kong  (孔 锐)
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Xiao-hui Zhang  (张晓慧)
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Jian-hua Gong  (龚建华)
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Ran-ran Song  (宋然然)
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jian-hua Gong  (龚建华).

Additional information

Both authors contributed equally to this work.

This work was supported by grants from the Fundamental Research Funds for the Central Universities (HUST No. 2015TS096), Hubei Province Health and Family Planning Scientific Research Project (No. WJ2015MB019), and a funding program of Science and Technology Projects of Shenzhen (No. JCYJ20150403142731429).

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wang, J., Li, L., Shao, Ss. et al. Association analysis of genetic variant of rs13331 in PSD95 gene with autism spectrum disorders: A case-control study in a Chinese population. J. Huazhong Univ. Sci. Technol. [Med. Sci.] 36, 285–288 (2016). https://doi.org/10.1007/s11596-016-1581-z

Download citation

  • Received:

  • Revised:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11596-016-1581-z

Key words

Search

Navigation