Identifying environmental risk factors and gene-environment interactions in holoprosencephaly.

Autor: Addissie YA; Medical Genetics Branch, National Human Genome Research Institute, The National Institutes of Health, Bethesda, Maryland, USA., Troia A; Cardiovascular & Pulmonary Branch, National Heart, Lung, and Blood Institute, The National Institutes of Health, Bethesda, Maryland, USA., Wong ZC; Cardiovascular & Pulmonary Branch, National Heart, Lung, and Blood Institute, The National Institutes of Health, Bethesda, Maryland, USA., Everson JL; Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA.; Molecular and Environmental Toxicology Center, University of Wisconsin-Madison, Madison, Wisconsin, USA., Kozel BA; Cardiovascular & Pulmonary Branch, National Heart, Lung, and Blood Institute, The National Institutes of Health, Bethesda, Maryland, USA., Muenke M; Medical Genetics Branch, National Human Genome Research Institute, The National Institutes of Health, Bethesda, Maryland, USA., Lipinski RJ; Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA.; Molecular and Environmental Toxicology Center, University of Wisconsin-Madison, Madison, Wisconsin, USA., Malecki KMC; Molecular and Environmental Toxicology Center, University of Wisconsin-Madison, Madison, Wisconsin, USA.; Department of Population Health Sciences, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, USA., Kruszka P; Medical Genetics Branch, National Human Genome Research Institute, The National Institutes of Health, Bethesda, Maryland, USA.
Jazyk: angličtina
Zdroj: Birth defects research [Birth Defects Res] 2021 Jan 01; Vol. 113 (1), pp. 63-76. Date of Electronic Publication: 2020 Oct 28.
DOI: 10.1002/bdr2.1834
Abstrakt: Background: Holoprosencephaly is the most common malformation of the forebrain (1 in 250 embryos) with severe consequences for fetal and child development. This study evaluates nongenetic factors associated with holoprosencephaly risk, severity, and gene-environment interactions.
Methods: For this retrospective case control study, we developed an online questionnaire focusing on exposures to common and rare toxins/toxicants before and during pregnancy, nutritional factors, maternal health history, and demographic factors. Patients with holoprosencephaly were primarily ascertained from our ongoing genetic and clinical studies of holoprosencephaly. Controls included children with Williams-Beuren syndrome (WBS) ascertained through online advertisements in a WBD support group and fliers.
Results: Difference in odds of exposures between cases and controls as well as within cases with varying holoprosencephaly severity were studied. Cases included children born with holoprosencephaly (n = 92) and the control group consisted of children with WBS (n = 56). Pregnancy associated risk associated with holoprosencephaly included maternal pregestational diabetes (9.2% of cases and 0 controls, p = .02), higher alcohol consumption (adjusted odds ratio [aOR], 1.73; 95% CI, 0.88-15.71), and exposure to consumer products such as aerosols or sprays including hair sprays (aOR, 2.46; 95% CI, 0.89-7.19). Significant gene-environment interactions were identified including for consumption of cheese (p < .05) and espresso drinks (p = .03).
Conclusion: The study identifies modifiable risk factors and gene-environment interactions that should be considered in future prevention of holoprosencephaly. Studies with larger HPE cohorts will be needed to confirm these findings.
(© 2020 Wiley Periodicals LLC.)
Databáze: MEDLINE
Externí odkaz: