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AHR gene-dioxin interactions and birthweight in the Seveso Second Generation Health Study.
- Source :
-
International journal of epidemiology [Int J Epidemiol] 2018 Dec 01; Vol. 47 (6), pp. 1992-2004. - Publication Year :
- 2018
-
Abstract
- Background: 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD) is proposed to interfere with fetal growth via altered activity of the aryl hydrocarbon receptor (protein: AHR; gene: AHR) pathway which regulates diverse biological and developmental processes including xenobiotic metabolism. Genetic variation in AHR is an important driver of susceptibility to low birthweight in children exposed to prenatal smoking, but less is known about these genetic interactions with TCDD, AHR's most potent xenobiotic ligand.<br />Methods: The Seveso Women's Health Study (SWHS), initiated in 1996, is a cohort of 981 Italian women exposed to TCDD from an industrial explosion in July 1976. We measured TCDD concentrations in maternal serum collected close to the time of the accident. In 2008 and 2014, we followed up the SWHS cohort and collected data on birth outcomes of SWHS women with post-accident pregnancies. We genotyped 19 single nucleotide polymorphisms (SNPs) in AHR among the 574 SWHS mothers.<br />Results: Among 901 singleton births, neither SNPs nor TCDD exposure alone were significantly associated with birthweight. However, we found six individual SNPs in AHR which adversely modified the association between maternal TCDD and birthweight, implicating gene-environment interaction. We saw an even stronger susceptibility to TCDD due to interaction when we examined the joint contribution of these SNPs in a risk allele score. These SNPs were all located in noncoding regions of AHR, particularly in proximity to the promoter.<br />Conclusions: This is the first study to demonstrate that genetic variation across the maternal AHR gene may shape fetal susceptibilities to TCDD exposure.
- Subjects :
- Cohort Studies
Environmental Exposure adverse effects
Environmental Pollutants metabolism
Environmental Pollutants toxicity
Female
Fetal Development drug effects
Fetal Development genetics
Genetic Predisposition to Disease
Humans
Infant, Newborn
Italy epidemiology
Polychlorinated Dibenzodioxins metabolism
Polymorphism, Single Nucleotide
Pregnancy
Teratogens metabolism
Teratogens toxicity
Women's Health
Xenobiotics metabolism
Basic Helix-Loop-Helix Transcription Factors genetics
Basic Helix-Loop-Helix Transcription Factors metabolism
Birth Weight drug effects
Polychlorinated Dibenzodioxins toxicity
Receptors, Aryl Hydrocarbon genetics
Receptors, Aryl Hydrocarbon metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1464-3685
- Volume :
- 47
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- International journal of epidemiology
- Publication Type :
- Academic Journal
- Accession number :
- 30124847
- Full Text :
- https://doi.org/10.1093/ije/dyy165