beta2-Adrenergic receptor gene variants and risk for autism in the AGRE cohort.
ABSTRACT The beta2-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.
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ABSTRACT: The goal of this review was to evaluate the association of β2-adrenergic receptor (ADRB2) gene polymorphisms with asthma and obesity. Asthma is the most common pediatric inflammatory disorder. The prevalence, severity, and hospitalization index for asthma have increased markedly in the last several decades. Interestingly, asthma is often diagnosed along with obesity. Genetic factors are essential for both conditions, and some of the candidate pleiotropic genes thought to be involved in the development of these diseases are ADRB2, vitamin D receptor (VDR), leptin (LEP), protein kinase C alpha (PRKCA), and tumor necrosis factor alpha (TNFα). The ADRB2 has been studied in multiple populations and more than 80 polymorphisms, mainly single-nucleotide polymorphisms, have been identified. For nonsynonymous Arg16Gly, Gln27Glu, and Thr164Ile, functional effects have been shown. In vivo, these polymorphisms have been evaluated to determine their association with both obesity and asthma, but the results are inconsistent and depend on the population studied or how the disease was defined. Currently, there are only few reports describing the genetic background for the comorbidity of asthma and obesity.Pediatric Allergy, Immunology, and Pulmonology 09/2014; 27(3):104-110. · 0.56 Impact Factor
- 09/2011; , ISBN: 978-953-307-558-7
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ABSTRACT: Existing literature indicates that ADRB2 gene is associated with health and longevity, but none of previous studies investigated associations of carrying the ADRB2 minor alleles and interactions between ADRB2 genotypes and social/behavioral factors(GxE) with health outcomes at advanced ages. This study intends to fill in this research gap. We conducted an exploratory analysis, using longitudinal survey phenotype/genotype data from 877 oldest-old aged 90+. To estimate association of GxE interactions with health outcome, adjusted for the potential correlation between genotypes and social/behavioral factors and various other potentially confounding factors, we develop and test an innovative three-step procedure which combines logistic regression and structural equation methods. Interaction between regular exercise and carrying rs1042718 minor allele is significantly and positively associated with good cognitive function; interaction between regular exercise and carrying rs1042718 or rs1042719 minor allele is significantly and positively associated with self-reported good health; and interaction between social-leisure activities and carrying rs1042719 minor allele is significantly and positively associated with self-reported good health. Carrying rs1042718 or rs1042719 minor alleles is significantly and negatively associated with negative emotion, but the ADRB2 SNPs are not significantly associated with cognitive function and self-reported health. Our structural equation analysis found that, adjusted for the confounding effects of correlation of the ADRB2 SNPs with negative emotion, interaction between negative emotion and carrying rs1042718 or rs1042719 minor allele is significantly and negatively associated with cognitive function. The positive association of regular exercise and social-leisure activities with cognitive function and self-reported health, and negative association of negative emotion with cognitive function, were much stronger among carriers of rs1042718 or rs1042719 alleles, compared to the non-carriers. The results indicate significant positive associations of interactions between social/behavioral factors and the ADRB2 genotypes with health outcomes of cognitive function and self-reported health, and negative associations of carrying rs1042718 or rs1042719 minor alleles with negative emotion, at advanced ages in China. Our findings are exploratory rather than causal conclusions. This study implies that near-future health promotion programs considering individuals' genetic profiles, with appropriate protection of privacy/confidentiality, would yield increased benefits and reduced costs to the programs and their participants.BMC Geriatrics 09/2013; 13(1):91. · 2.34 Impact Factor