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

Abstract

The b 2 -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.

Quantitative mRNA Analysis of Serotonin 5-HT₄ and Adrenergic β₂ Receptors in the Mouse Embryonic Telencephalon

“…Studies have shown that 5-HT 4 -Rs and ␤ 2 -ARs may play important roles in the neurobiology of depressive disorders [Mongeau et al, 1997;Sastre et al, 2001;Duman, 2007;Lucas et al, 2007;Tamburella et al, 2009], Alzheimer's disease [Lezoualc'h, 2007;Yu et al, 2008Yu et al, , 2010, and autism spectrum disorders [Connors et al, 2005;Cheslack-Postava et al, 2007;Janušonis, 2008;Vincent et al, 2009;Slaten et al, 2010].…”

“…Since 5-HT 4 -Rs receptors may interact with ␤ 2 -ARs during embryonic and fetal development and ␤ 2 -ARs can detect stress-related signals, the ontogeny of 5-HT 4 -R and ␤ 2 -AR levels in the developing forebrain has potentially important implications for understanding autism spectrum and other developmental disorders [Cheslack-Postava et al, 2007;Vincent et al, 2009;Yirmiya and Charman, 2010]. In the present study, we used quantitative reverse-transcription polymerase chain reaction (qRT-PCR) to measure the expression levels of all 5-HT 4 -R splice variants and ␤ 2 -AR in the embryonic mouse telencephalon from embryonic day 13 to birth.…”

The Epidemiology of Autism Spectrum Disorders

“…Consequently, prenatal environmental exposures and gene-environment interactions involving maternal genes, such as those contributing to regulation of the intrauterine environment or detoxification of exogenous exposures during gestation, could be of prime etiologic significance. The exploration of these direct maternal genetic effects has already begun in some candidate gene studies on the basis of case-parent trio data (24), although optimal designs to test these hypotheses involve the collection of additional genotypic data on grandparents (110). Furthermore, studies of endogenous biomarkers such as the neurotrophic, immune, and endocrine factors, in utero, at birth, and very early in life could also offer clues about dysregulated processes that might, in turn, lead to investigations of candidate genes or specific exposures known to influence these pathways.…”

What the Genetic Background of Individuals with Asthma and Obesity Can Reveal: Is β2-Adrenergic Receptor Gene Polymorphism Important?

“…7 Between commonly shared genes, the most biologicaly plausible are those that are pleiotropic, including b2-adrenergic receptor (ADRB2), vitamin D receptor gene (VDR), leptin (LEP), protein kinase C alpha (PRKCA), and tumor necrosis factor a (TNFa). [8][9][10][11][12] Polymorphisms within ADRB2 were described in association with different disorders, including not only asthma and obesity but also hypertension, 13 autism, 14 cerebral palsy, 15 susceptibility to parasite infestation, 16 and rheumatoid arthritis. 17 The ADRB2 Gene…”