β2-Adrenergic receptor gene variants and risk for autism in the AGRE cohort

被引：0
作者：
K Cheslack-Postava
M D Fallin
D Avramopoulos
S L Connors
A W Zimmerman
C G Eberhart
C J Newschaffer
机构：
[1] Johns Hopkins Bloomberg School of Public Health,Department of Epidemiology
[2] Johns Hopkins University,Department of Psychiatry and Institute of Genetic Medicine
[3] Kennedy Krieger Institute,Department of Neurology and Developmental Medicine
[4] Johns Hopkins University School of Medicine,Department of Pathology
来源：
Molecular Psychiatry | 2007年 / 12卷
关键词：
association study; autistic disorder; beta-2 adrenergic receptors; effect modification; single nucleotide polymorphism; stress;
D O I：
暂无
中图分类号：
学科分类号：
摘要：
The β2-adrenergic receptor is part of the catecholamine system, and variants at two polymorphic sites in the gene coding for the receptor (ADRB2) confer increased activity. Overstimulation of this receptor may alter brain development, and has been linked to autism in non-identical twins. The objective of this study was to determine whether alleles in ADRB2 are associated with diagnosis of autism in the Autism Genetic Resource Exchange (AGRE) population. Three hundred and thirty-one independent autism case–parent trios were included in the analysis. Subjects were genotyped at activity-related polymorphisms rs1042713 (codon 16) and rs1042714 (codon 27). Association between autism and genotypes at each polymorphic site was tested using genotype-based transmission disequilibrium tests, and effect modification by family and pregnancy characteristics was evaluated. Sensitivity to designation of the proband in each family was assessed by performing 1000 repeats of the analysis selecting affected children randomly. A statistically significant OR of 1.66 for the Glu27 homozygous genotype was observed. Increased associations with this genotype were observed among a subset of Autism Diagnostic Observation Schedule confirmed cases and a subset reporting experience of pregnancy-related stressors. In conclusion, the Glu27 allele of the ADRB2 gene may confer increased risk of autism and shows increased strength with exposure to pregnancy related stress.
引用
收藏
页码：283 / 291
页数：8
相关论文
共 269 条
  • [1] Arndt TL(2005)The teratology of autism Int J Dev Neurosci 23 189-199
  • [2] Stodgell CJ(1998)Why do neurotransmitters act like growth factors? Perspect Dev Neurobiol 5 323-335
  • [3] Rodier PM(1987)Beta-adrenergic binding sites in fetal rat central nervous system and pineal gland: their relation to other receptor sites Dev Pharmacol Ther 10 422-435
  • [4] Weiss ER(1994)Beta-adrenergic receptor overexpression in the fetal rat: distribution, receptor subtypes, and coupling to adenylate cyclase activity via G-proteins Toxicol Appl Pharmacol 129 223-234
  • [5] Maness P(2003)Developmental toxicity of terbutaline: critical periods for sex-selective effects on macromolecules and DNA synthesis in rat brain, heart, and liver Brain Res Bull 59 319-329
  • [6] Lauder JM(2004)Terbutaline is a developmental neurotoxicant: effects on neuroproteins and morphology in cerebellum, hippocampus, and somatosensory cortex J Pharmacol Exp Ther 308 529-537
  • [7] Schlumpf M(1989)Prenatal terbutaline exposure in the rat: selective effects on development of noradrenergic projections to cerebellum Brain Res Bull 23 263-265
  • [8] Bruinink A(1990)Fetal terbutaline exposure causes selective postnatal increases in cerebellar alpha-adrenergic receptor binding Life Sci 47 2051-2057
  • [9] Lichtensteiger W(2005)Beta2-adrenergic receptor activation and genetic polymorphisms in autism: data from dizygotic twins J Child Neurol 20 876-884
  • [10] Cortes R(2003)Ontogenesis of beta-adrenoceptor signaling: implications for perinatal physiology and for fetal effects of tocolytic drugs J Pharmacol Exp Ther 306 1-7
12345678910