Abstract
Impairment in social reciprocity is a central component of autism. In preclinical studies, arginine vasopressin (AVP) has been shown to increase a range of social behaviors, including affiliation and attachment, via the V1a receptor (AVPR1A) in the brain. Both the behavioral effects of AVP and the neural distribution of the V1a receptor vary greatly across mammalian species. This difference in regional receptor expression as well as differences in social behavior may result from a highly variable repetitive sequence in the 5′ flanking region of the V1a gene (AVPR1A). Given this comparative evidence for a role in inter-species variation in social behavior, we explored whether within our own species, variation in the human AVPR1A may contribute to individual variations in social behavior, with autism representing an extreme form of social impairment. We genotyped two microsatellite polymorphisms from the 5′ flanking region of AVPR1A for 115 autism trios and found nominally significant transmission disequilibrium between autism and one of the microsatellite markers by Multiallelic Transmission/Disequilibrium test (MTDT) that was not significant after Bonferroni correction. We also screened approximately 2 kb of the 5′ flanking region and the coding region and identified 10 single nucleotide polymorphisms.
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References
Insel TR, Young LJ . Neuropeptides and the evolution of social behavior Curr Opin Neurobiol 2000 10: 784–789
Young LJ, Nilsen R, Waymire KG, MacGregor GR, Insel TR . Increased affiliative response to vasopressin in mice expressing the V1a receptor from a monogamous vole Nature 1999 400: 766–768
Born J, Pietrowsky R, Fehm H . Neuropsychological effects of vasopressin in healthy humans Prog in Brain Res 1998 119: 619–643
Thibonnier M, Graves MK, Wagner MS, Auzan C, Clauser E, Willard HF . Structure, sequence, expression, and chromosomal localization of the human V1a vasopressin receptor gene Genomics 1996 31: 327–334
Thibonnier M, Graves MK, Wagner MS, Chatelain N, Soubrier F, Corvol P et al. Study of V(1)-vascular vasopressin receptor gene microsatellite polymorphisms in human essential hypertension J Mol Cell Cardiol 2000 32: 557–564
Lord C, Rutter M, Le Couteur A . Autism Diagnostic Interview – Revised: a revised version of a diagnostic interview for caregivers of individuals with possible pervasive developmental disorders J Autism Dev Disord 1994 24: 659–685
Lord C, Risi S, Lambrecht L, Cook EH Jr, Leventhal BL, DiLavore PC et al. The autism diagnostic observation schedule-generic: a standard measure of social and communication deficits associated with the spectrum of autism J Autism Dev Disord 2000 30: 205–223
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders (4th edn) American Psychiatric Association Press: Washington DC 1994
O'Connell JR, Weeks DE . PedCheck: a program for identification of genotype incompatibilities in linkage analysis Am J Hum Genet 1998 63: 259–266
Spielman R, Ewens W . The TDT and other family-based tests for linkage disequilibrium and association Am J Hum Genet 1996 59: 983–989
Cook EH Jr, Courchesne R, Lord C, Cox NJ, Yan S, Lincoln A et al. Evidence of linkage between the serotonin transporter and autistic disorder Mol Psychiatry 1997 2: 247–250
Cook EH Jr, Courchesne RY, Cox NJ, Lord C, Gonen D, Guter SJ et al. Linkage-disequilibrium mapping of autistic disorder, with 15q11–13 markers Am J Hum Genet 1998 62: 1077–1083
Wassink T, Piven J, Vieland V, Huang J, Swiderski R, Pietila J et al. Evidence supporting WNT2 as an autism susceptibility gene Am J Med Genet (Neuropsychiatr Genet) 2001 105: 406–413
Persico A, D'Agruma L, Maiorano N, Totaro A, Militerni R, Bravaccio C et al. Reelin gene alleles and haplotypes as a factor predisposing to autistic disorder Mol Psychiatry 2001 6: 150–159
Ingram JL, Stodgell CJ, Hyman SL, Figlewicz DA, Weitkamp LR, Rodier PM . Discovery of allelic variants of HOXA1 and HOXB1: genetic susceptibility to autism spectrum disorders Teratology 2000 62: 393–405
Buxbaum J, Silverman J, Smith C, Greenberg D, Kilifarski M, Reichardt J et al. Association between a γ-aminobutyric acid receptor subunit gene polymorphism and autism Mol Psychiatry 2002 7: 311–316
Klauck SM, Poustka F, Benner A, Lesch K-P, Poustka A . Serotonin transporter (5-HTT) gene variants associated with autism? Hum Molec Genet 1997 6: 2233–2238
Yirmiya N, Pilowsky T, Nemanov L, Arbelle S, Feinsilver T, Fried I et al. Evidence for an association with the serotonin transporter promoter region polymorphism and autism Am J Med Genet (Neuropsychiatr Genet) 2001 105: 381–386
Tordjman S, Gutneckt L, Carlier M, Spitz E, Antoine C, Slama F et al. Role of the serotonin transporter in the behavioral expression of autism Mol Psychiatry 2001 6: 434–439
Kim S-J, Cox N, Courchesne R, Lord C, Corsello C, Akshoomoff N et al. Transmission disequilibrium mapping in the serotonin transporter gene (SLC6A4) region in autistic disorder Mol Psychiatry 2002 7: 278–288
Pritchard JK . Are rare variants responsible for susceptibility to complex diseases? Am J Hum Genet 2001 69: 124–137
Darnell JC, Jensen KB, Jin P, Brown V, Warren ST, Darnell RB . Fragile X mental retardation protein targets G quartet mRNAs important for neuronal function Cell 2001 107: 489–499
Acknowledgements
This work was supported, in part, by NIH grants R01 MH56538 (TI), K02 MH01389 (EHC), R01 MH52223 (EC, EHC), PO1 HD35482 (EHC, CL), NSF grant IBN9876754 (TI), the Jean Young and Walden W Shaw Foundation (BLL), the Harris Foundation (BLL), and the Brain Research Foundation (EHC).
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Kim, SJ., Young, L., Gonen, D. et al. Transmission disequilibrium testing of arginine vasopressin receptor 1A (AVPR1A) polymorphisms in autism. Mol Psychiatry 7, 503–507 (2002). https://doi.org/10.1038/sj.mp.4001125
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DOI: https://doi.org/10.1038/sj.mp.4001125
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