Association study in siblings and case-controls of serotonin- and oxytocin-related genes with high functioning autism

详细信息    查看全文

• 作者：Johanna Nyffeler (1)
  Susanne Walitza (1) (2)
  Elise Bobrowski (1) (3)
  Ronnie Gundelfinger (1)
  Edna Grünblatt (1) (2)
  
• 关键词：Autism spectrum disorder ; High functioning autism ; Oxytocin receptor ; Polymorphism ; Serotonin receptor 2A ; Serotonin transporter
• 刊名：Journal of Molecular Psychiatry
• 出版年：2014
• 出版时间：December 2014
• 年：2014
• 卷：2
• 期：1
• 全文大小：258 KB
• 作者单位：Johanna Nyffeler (1)
  Susanne Walitza (1) (2)
  Elise Bobrowski (1) (3)
  Ronnie Gundelfinger (1)
  Edna Grünblatt (1) (2)
  
  1. University Clinics of Child and Adolescent Psychiatry (UCCAP), University of Zurich, Thurgauerstr. 39, CH-8050, Zurich, Switzerland
  2. Neuroscience Center Zurich, University of Zurich and ETH Zurich, Zurich, Switzerland
  3. Department of Experimental Psychology, University of Regensburg, Regensburg, Germany
  
• ISSN：2049-9256

文摘

Background Autism spectrum disorder (ASD) is heritable and neurodevelopmental with unknown causes. The serotonergic and oxytocinergic systems are of interest in autism for several reasons: (i) Both systems are implicated in social behavior, and abnormal levels of serotonin and oxytocin have been found in people with ASD; (ii) treatment with selective serotonin reuptake inhibitors and oxytocin can yield improvements; and (iii) previous association studies have linked the serotonin transporter (SERT; SLC6A4), serotonin receptor 2A (HTR2A), and oxytocin receptor (OXTR) genes with ASD. We examined their association with high functioning autism (HFA) including siblings and their interaction. Methods In this association study with HFA children (IQ-gt;-0), siblings, and controls, participants were genotyped for four single nucleotide polymorphisms (SNPs) in OXTR (rs2301261, rs53576, rs2254298, rs2268494) and one in HTR2A (rs6311) as well as the triallelic HTTLPR (SERT polymorphism). Results We identified a nominal significant association with HFA for the HTTLPR s allele (consisting of S and LG alleles) (p--040; odds ratio (OR)--.697, 95% CI 1.191-.204)). Four polymorphisms (HTTLPR, HTR2A rs6311, OXTR rs2254298 and rs53576) in combination conferred nominal significant risk for HFA with a genetic score of ? (OR--.09, 95% CI 1.05-.18, p--037). The resulting area under the receiver operating characteristic curve was 0.595 (p--033). Conclusions Our findings, combined with those of previous reports, indicate that ASD, in particular HFA, is polygenetic rather than monogenetic and involves the serotonergic and oxytocin pathways, probably in combination with other factors.