Journal Mobile Options
Table of Contents
Vol. 54, No. 3, 2006
Issue release date: March 2007
Neuropsychobiology 2006;54:160–165

Association of GABRB3 Polymorphisms with Autism Spectrum Disorders in Korean Trios

Kim S.A. · Kim J.H. · Park M. · Cho I.H. · Yoo H.J.
aDepartment of Pharmacology, School of Medicine, bDivision of Biostatistics, School of Medicine, Eulji University, Daejeon, cDepartment of Neuropsychiatry, Gachon Medical School, Incheon, and dDepartment of Psychiatry, Seoul National University Bundang Hospital, Seongnam, South Korea

Individual Users: Register with Karger Login Information

Please create your User ID & Password

Contact Information

I have read the Karger Terms and Conditions and agree.

To view the fulltext, please log in

To view the pdf, please log in


Background/Aims: Autism spectrum disorders (ASD) are complex neuropsychiatric disorders having a genetic risk factor. The association and linkage study for the γ-aminobutyric acid type A receptor β3 subunit gene (GABRB3), located within the chromosome 15q11-q13 autism candidate region, and ASD have been evaluated. The aim of this study was to investigate the association between GABRB3 and ASD in the Korean population. Methods: The present study was conducted with the detection of four single-nucleotide polymorphisms (rs1426217, rs2081648, rs890317, rs981778) in GABRB3 and association analysis in 104 Korean ASD trios using the transmission disequilibrium test. Results: The transmission disequilibrium test demonstrated that an allele at rs2081648 showed preferential transmission (p = 0.027). One haplotype, including all examined markers in GABRB3, demonstrated significant association (p = 0.043), but the global χ2 test for haplotype transmission did not reveal an association between GABRB3 and ASD (χ2 = 15.516, d.f. = 15). Conclusion: Our finding suggested that single-nucleotide polymorphisms in GABRB3 may play a significant role in the genetic predisposition to ASD in the Korean population.

Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.


  1. American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders DSM-IV, ed 4. Washington, American Psychiatric Association, 1994.
  2. Chakrabarti S, Fombonne E: Pervasive developmental disorders in preschool children. JAMA 2001;285:3093–3099.
  3. Charman T: The prevalence of autism spectrum disorders: recent evidence and future challenges. Eur Child Adolesc Psychiatry 2002;11:249–256.
  4. Yonan AL, Alarcon M, Cheng R, Magnusson PK, Spence SJ, Palmer AA, Grunn A, Juo SH, Terwilliger JD, Liu J, Cantor RM, Geschwind DH, Gilliam TC: A genomewide screen of 345 families for autism-susceptibility loci. Am J Hum Genet 2003;73:886–897.
  5. Bailey A, Le Couteur A, Gottesman I, Bolton P, Simonoff E, Yuzda E, Rutter M: Autism as a strongly genetic disorder: evidence from a British twin study. Psychol Med 1995;25:63–77.
  6. Folstein S, Rutter M: Infantile autism: a genetic study of 21 twin pairs. J Child Psychol Psychiatry 1997;18:297–321.

    External Resources

  7. Steffenburg S, Gillberg C, Hellgren L, Andersson L, Gillberg IC, Jakobsson G, Bohman M: A twin study of autism in Denmark, Finland, Iceland, Norway and Sweden. J Child Psychol Psychiatry 1989;30:405–416.
  8. Pickles A, Bolton P, Macdonald H, Bailey A, Le Couteur A, Sim CH, Rutter M: Latent-class analysis of recurrence risks for complex phenotypes with selection and measurement error: a twin and family history study of autism. Am J Hum Genet 1995;57:717–726.
  9. Weeks DE, Lathrop GM: Polygenic disease: methods for mapping complex disease traits. Trends Genet 1995;11:513–519.
  10. Gillberg C: Chromosomal disorders and autism. J Autism Dev Disord 1998;28:415–425.
  11. Bolton PF, Veltman MW, Weisblatt E, Holmes JR, Thomas NS, Youings SA, Thompson RJ, Roberts SE, Dennis NR, Browne CE, Goodsoon S, Moore V, Brown J: Chromosome 15q11–13 abnormalities and other medical conditions in individuals with autism spectrum disorders. Psychiatr Genet 2004;14:131–137.
  12. Knoll JH, Wagstaff J, Lalande M: Cytogenetic and molecular studies in the Prader-Willi and Angelman syndromes: an overview. Am J Med Genet 1993;46:2–6.
  13. Ozcelik T, Leff S, Robinson W, Donlon T, Lalande M, Sanjines E, Schinzel A, Francke U: Small nuclear ribonucleoprotein polypeptide N (SNRPN), an expressed gene in the Prader-Willi syndrome critical region. Nat Genet 1992;2:265–269.
  14. Arrieta I, Lobato MN, Martinez B, Criado B: Parental origin of Robertsonian translocation (15q22q) and Prader Willi syndrome associated with autism. Psychiatr Genet 1994;4:63–65.
  15. Dykens EM, Sutcliffe JS, Levitt P: Autism and 15q11–q13 disorders: behavioral, genetic, and pathophysiological issues. Ment Retard Dev Disabil Res Rev 2004;10:284–291.
  16. Graham JM, Rosner B, Dykens E, Visootsak J: Behavioral features of CHARGE syndrome (Hall-Hittner syndrome) comparison with Down syndrome, Prader-Willi syndrome, and Williams syndrome. Am J Med Genet 2005;133:240–247.

    External Resources

  17. Mohandas TK, Park JP, Spellman RA, Filiano JJ, Mamourian AC, Hawk AB, Belloni DR, Noll WW, Moeschler JB: Paternally derived de novo interstitial duplication of proximal 15q in a patient with developmental delay. Am J Med Genet 1999;82:294–300.
  18. Bass MP, Menold MM, Wolpert CM, Donnelly SL, Ravan SA, Hauser ER, Maddox LO, Vance JM, Abramson RK, Wright HH, Gilbert JR, Cuccaro ML, DeLong GR, Pericak-Vance MA: Genetic studies in autistic disorder and chromosome 15. Neurogenetics 2000;2:219–226.
  19. Philippe A, Martinez M, Guilloud-Bataille M, Gillberg C, Rastam M, Sponheim E, Coleman M, Zapella M, Aschauer H, Van Maldergem L, Penet C, Feingold J, Brice A, Leboyer M: The Paris Autism Research International Sibpair Study, genome-wide scan for autism susceptibility genes. Hum Mol Genet 1999;8:805–812.
  20. Buxbaum JD, Silverman JM, Smith CJ, Greenberg DA, Kilifarski M, Reichert J, Cook EH, Fang Y, Song CY, Vitale R: Association between a GABRB3 polymorphism and autism. Mol Psychiatry 2002;7:311–316.
  21. Cook EH, Courchesne RY, Cox NJ, Lord C, Gonen D, Guter SJ, Lincoln A, Nix K, Haas R, Leventhal BL, Courchesne E: Linkage-disequilibrium mapping of autistic disorder, with 15q11–13 markers. Am J Hum Genet 1998;62:1077–1083.
  22. McCauley JL, Olson LM, Delahanty R, Amin T, Nurmi EL, Organ EL, Jacobs MM, Folstein SE, Haines JL, Sutcliffe JS: A linkage disequilibrium map of the 1-Mb 15q12 GABAA receptor subunit cluster and association to autism. Am J Med Genet 2004;131:51–59.

    External Resources

  23. Menold MM, Shao Y, Wolpert CM, Donnelly SL, Raiford KL, Martin ER, Ravan SA, Abramson RK, Wright HH, Delong GR, Cuccaro ML, Pericar-Vance MA, Gilbert JR: Association analysis of chromosome 15 GABAA receptor subunit genes in autistic disorder. J Neurogenet 2001;15:245–259.
  24. Lord C, Rutter M, DiLavore P, Risi S: Autism Diagnostic Observation Schedule, Los Angeles, Western Psychological Services, 2002.
  25. Rutter M, Le Couteur A, Lord C: Autism Diagnostic Interview – Revised. Los Angeles, Western Psychological Services, 2003.
  26. Kim SK, Kim OK: Korean Vineland Social Maturity Scale, ed 4. Seoul, Chung-Ang Jeokseong Press, 2002.
  27. Park KS, Yoon JR, Park HJ, Park HJ, Kwon KO: Korean Educational Developmental Institute – Wechsler Intelligence Scale for Children (KEDI-WISC), ed 2. Seoul, Korean Educational Development Institute, 2002.
  28. Ding K, Zhou K, He F, Shen Y: LDA – a java-based linkage disequilibrium analyzer. Bioinformatics 2003;19:2147–2148.
  29. Clayton D: A generalization of the transmission/disequilibrium test for uncertain-haplotype transmission. Am J Hum Genet 1999;65:1170–1177.
  30. Veenstra-Vanderweele J, Cook EH, Lombroso PJ: Genetics of childhood disorders. XLVI. Autism, part 5: genetics of autism. J Am Acad Child Adolesc Psychiatry 2003;42:116–118.
  31. Cohen BI: Elevated levels of plasma and urine gamma-aminobutyric acid – a case study for an autistic child. Autism 1999;3:437–440.

    External Resources

  32. Rolf LH, Haarmann FY, Grotemeyer KH, Kehrer H: Serotonin and amino acid content in platelets of autistic children. Acta Psychiatr Scand 1993;87:312–316.
  33. Dhossche D, Applegate H, Abraham A, Maertens P, Bland L, Bencsath A, Martinez J: Elevated plasma gamma-aminobutyric acid (GABA) levels in autistic youngsters: stimulus for a GABA hypothesis of autism. Med Sci Monit 2002;8:PR1–PR6.
  34. Blatt GJ, Fitzgerald CM, Guptill JT, Booker AB, Kemper TL, Bauman ML: Density and distribution of hippocampal neurotransmitter receptors in autism: an autoradiographic study. J Autism Dev Disord 2001;31:537–543.
  35. Chugani DC, Muzik O, Juhasz C, Janisse JJ, Ager J, Chugani HT: Postnatal maturation of human GABAA receptors measured with positron emission tomography. Ann Neurol 2001;49:618–626.
  36. Barnard EA: The molecular biology of GABAA receptors and their structural determinants. Adv Biochem Psychopharmacol 1995;48:1–16.
  37. Fritschy JM, Mohler H: GABAA-receptor heterogeneity in the adult rat brain: differential regional and cellular distribution of seven major subunits. J Comp Neurol 1995;359:154–194.
  38. Holopainen IE, Metsahonkala EL, Kokkonen H, Parkkola RK, Manner TE, Nagren K, Korpi ER: Decreased binding of [11C]flumazenil in Angelman syndrome patients with GABAA receptor beta3 subunit deletions. Ann Neurol 2001;49:110–113.
  39. DeLorey TM, Handforth A, Anagnostaras SG, Homanics GE, Minassian BA, Asatourian A, Fanselow MS, Delgado-Escueta A, Ellison GD, Olsen RW: Mice lacking the beta3 subunit of the GABAA receptor have the epilepsy phenotype and many of the behavioral characteristics of Angelman syndrome. J Neurosci 1998;18:8505–8514.
  40. DeLorey TM, Olsen RW: GABA and epileptogenesis: comparing gabrb3 gene-deficient mice with Angelman syndrome in man. Epilepsy Res 1999;36:123–132.
  41. Homanics GE, DeLorey TM, Firestone LL, Quinlan JJ, Handforth A, Harrison NL, Krasowski MD, Rick CE, Korpi ER, Makela R, Brilliant MH, Hagiwara N, Ferguson C, Snyder K, Olsen RW: Mice devoid of gamma-aminobutyrate type A receptor beta3 subunit have epilepsy, cleft palate, and hypersensitive behavior. Proc Natl Acad Sci USA 1997;94:4143–4148.
  42. Volkmar FR, Paul R, Klin A, Cohen D: Handbook of Autism and Pervasive Developmental Disorders, ed 3. Hoboken, John Wiley & Sons, 2005.
  43. Sadock BJ, Sadock VA: Synopsis of Psychiatry, ed 9. Philadelphia, Lippincott Williams & Wilkins, 2003.
  44. Olsen RW, Tobin AT: Molecular biology of GABAA receptors. FASEB J 1990;4:1469–1480.
  45. Evans DW, Canavera K, Kleinpeter FL, Maccubbin E, Taga K: The fears, phobias and anxieties of children with autism spectrum disorders and Down syndrome: comparisons with developmentally and chronologically age matched children. Child Psychiatry Hum Dev 2005;36:3–26.
  46. Gillott A, Furniss F, Walte A: Anxiety in high-functioning children with autism. Autism 2001;5:277–286.
  47. Muris P, Steerneman P, Merckelbach H, Holdrinet I, Meesters C: Comorbid anxiety symptoms in children with pervasive developmental disorders. J Anxiety Disord 1998;12:387–393.
  48. Sverd J: Psychiatric disorders in individuals with pervasive developmental disorder. J Psychiatr Pract 2002;9:111–127.

    External Resources

  49. Marrosu F, Marrosu G, Rachel MG, Biggio G: Paradoxical reactions elicited by diazepam in children with classic autism. Funct Neurol 1987;2:355–361.
  50. Maestrini E, Lai C, Marlow A, Matthews N, Wallace S, Bailey A, Cook EH, Weeks DE, Monaco AP: The International Molecular Genetic Study of Autism Consortium. Serotonin transporter (5-HTT) and gamma-aminobutyric acid receptor subunit beta3 (GABRB3) gene polymorphisms are not associated with autism in the IMGSA families. Am J Med Genet 1999;88:492–496.
  51. Martin ER, Menold MM, Wolpert CM, Bass MP, Donnelly SL, Ravan SA, Zimmerman A, Gilbert JR, Vance JM, Maddox LO, Wright HH, Abramson RK, DeLong GR, Cuccaro ML, Pericak-Vance MA: Analysis of linkage disequilibrium in gamma-aminobutyric acid receptor subunit genes in autistic disorder. Am J Med Genet 2000;96:43–48.

Pay-per-View Options
Direct payment This item at the regular price: USD 38.00
Payment from account With a Karger Pay-per-View account (down payment USD 150) you profit from a special rate for this and other single items.
This item at the discounted price: USD 26.50