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

  • Jia Wang (王 佳)
  • Li Li (李 丽)
  • Shan-shan Shao (邵珊珊)
  • Zhen He (何 珍)
  • Yan-lin Chen (陈艳琳)
  • Rui Kong (孔 锐)
  • Xiao-hui Zhang (张晓慧)
  • Jian-hua Gong (龚建华)Email author
  • Ran-ran Song (宋然然)


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.

Key words

polymorphism rs13331 PSD95 autism spectrum disorder 


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  1. 1.
    Sandin S, Lichtenstein P, Kuja-Halkola R, et al. The familial risk of autism. JAMA, 2014,311(17):1770–1777CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Elsabbagh M, Divan G, Koh YJ, et al. Global prevalence of autism and other pervasive developmental disorders. Autism Res, 2012,5(3):160–179CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Rumsey JM, Rapoport JL, Sceery WR. Autistic children as adults: psychiatric, social, and behavioral outcomes. J AmAcad Child Psychiatry, 1985,24(4):465–473CrossRefGoogle Scholar
  4. 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):68–74CrossRefPubMedPubMedCentralGoogle Scholar
  5. 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):755–766CrossRefPubMedGoogle Scholar
  6. 6.
    Baron-Cohen S. Social and pragmatic deficits in autism: cognitive or affective? J Autism Dev Disord, 1988,18(3): 379–402CrossRefPubMedGoogle Scholar
  7. 7.
    Eicher JD, Gruen JR. Language impairment and dyslexia genes influence language skills in children with autism spectrum disorders. Autism Res, 2014,8(2):229–234CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Helt M, Kelley E, Kinsbourne M, et al. Can children with autism recover? If so, how? Neuropsychol Rev, 2008,18(4):339–366CrossRefPubMedGoogle Scholar
  9. 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):44CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Ganz ML. The lifetime distribution of the incremental societal costs of autism. Arch Pediatr Adolesc Med, 2007,161(4):343–349CrossRefPubMedGoogle Scholar
  11. 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): 1807–1814CrossRefPubMedGoogle Scholar
  12. 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):202–208CrossRefGoogle Scholar
  13. 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):35–43CrossRefPubMedGoogle Scholar
  14. 14.
    Folstein S, Rutter M. Genetic influences and infantile autism. Nature, 1977,265(5596):726–728CrossRefPubMedGoogle Scholar
  15. 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):907–914CrossRefGoogle Scholar
  16. 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): 1357–1363CrossRefPubMedGoogle Scholar
  17. 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):1095–1102CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Zoghbi HY. Postnatal neurodevelopmental disorders: meeting at the synapse? Science, 2003,302(5646):826–830CrossRefPubMedGoogle Scholar
  19. 19.
    van Spronsen M, Hoogenraad CC. Synapse pathology in psychiatric and neurologic disease. Curr Neurol Neurosci Rep, 2010,10(3):207–214CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Gai X, Xie HM, Perin JC, et al. Rare structural variation of synapse and neurotransmission genes in autism. Mol Psychiatry, 2012,17(4):402–411CrossRefPubMedPubMedCentralGoogle Scholar
  21. 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):1809–1817CrossRefPubMedPubMedCentralGoogle Scholar
  22. 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):846–850CrossRefPubMedGoogle Scholar
  23. 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): e15107CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Chen J, Yu S, Fu Y, et al. Synaptic proteins and receptors defects in autism spectrum disorders. Front Cell Neurosci, 2014,8:276PubMedPubMedCentralGoogle Scholar
  25. 25.
    Taft CE, Turrigiano GG. PSD-95 promotes the stabilization of young synaptic contacts. Philos Trans R SocLond B BiolSci, 2014,369(1633):20130134CrossRefGoogle Scholar
  26. 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):433–439CrossRefPubMedGoogle Scholar
  27. 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):408–419CrossRefPubMedGoogle Scholar
  28. 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):839–849CrossRefPubMedGoogle Scholar
  29. 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):160–164CrossRefPubMedPubMedCentralGoogle Scholar
  30. 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):1591–1595Google Scholar
  31. 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):742–750CrossRefPubMedGoogle Scholar
  32. 32.
    Lord C, Cook EH, Leventhal BL, et al. Autism spectrum disorders. Neuron, 2000,28(2):355–363CrossRefPubMedGoogle Scholar
  33. 33.
    Kennedy MB. Signal-processing machines at the postsynaptic density. Science, 2000,290(5492):750–754CrossRefPubMedGoogle Scholar
  34. 34.
    Stephenson FA. Structure and trafficking of NMDA and GABAA receptors. BiochemSoc Trans, 2006,34(Pt 5):877–881Google Scholar
  35. 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):1203–1214CrossRefPubMedGoogle Scholar
  36. 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, S1CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Chen L, Chetkovich DM, Petralia RS, et al. Stargazin regulates synaptic targeting of AMPA receptors by two distinct mechanisms. Nature, 2000,408(6815):936–943CrossRefPubMedGoogle Scholar
  38. 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):71–82CrossRefPubMedGoogle Scholar
  39. 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):3645–3654CrossRefPubMedGoogle Scholar
  40. 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): e56688CrossRefPubMedPubMedCentralGoogle Scholar
  41. 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):1508–1517CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Huazhong University of Science and Technology and Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Jia Wang (王 佳)
    • 1
  • Li Li (李 丽)
    • 2
  • Shan-shan Shao (邵珊珊)
    • 1
  • Zhen He (何 珍)
    • 3
  • Yan-lin Chen (陈艳琳)
    • 2
  • Rui Kong (孔 锐)
    • 1
  • Xiao-hui Zhang (张晓慧)
    • 1
  • Jian-hua Gong (龚建华)
    • 1
    • 2
    Email author
  • Ran-ran Song (宋然然)
    • 1
  1. 1.Department of Maternal and Child Health and MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
  2. 2.Maternity and Children Health Care Hospital of Luohu DistrictShenzhenChina
  3. 3.Central Hospital of Longhua New DistrictShenzhenChina

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