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A Functional Aryl Hydrocarbon Receptor Genetic Variant, Alone and in Combination with Parental Exposure, is a Risk

Silvia Pulignani1, Andrea Borghini2, Cecilia Vecoli2

  • 1CNR Institute of Clinical Physiology, Via Moruzzi 1, 56124, Pisa, Italy. pulignani@ifc.cnr.it.

Cardiovascular Toxicology
|November 30, 2017
PubMed

Insights

The aryl hydrocarbon receptor (AhR) genetic variant p.Arg554Lys is linked to congenital heart disease (CHD) risk in humans. This variant interacts with parental exposures, like smoking and periconceptional factors, to increase CHD susceptibility.

Area of Science:

  • Cardiovascular Genetics
  • Developmental Biology
  • Toxicology

Background:

  • Aryl hydrocarbon receptor (AhR) signaling is crucial for heart development.
  • Experimental studies link AhR disruption to congenital heart disease (CHD), but human data is lacking.

Purpose of the Study:

  • To investigate the prevalence of a functional AhR genetic variant (p.Arg554Lys) in human CHD.
  • To assess the combined effects of this AhR variant and parental exposures on CHD risk.

Main Methods:

  • Genotyping of 128 CHD patients and 274 controls for the AhR p.Arg554Lys polymorphism using TaqMan assay.
  • Parental questionnaires on demographic, lifestyle, and preconception exposures.
  • Statistical analysis of genotype, allele distributions, and gene-environment interactions.

Main Results:

  • Significant differences in AhR p.Arg554Lys genotype and allele frequencies between CHD patients and controls (p < 0.001).
  • Elevated CHD risk associated with the AhR p.Arg554Lys variant under dominant and additive models (ORs 2.9-6.2).
  • Significant interactions between the 554-Lys allele and paternal smoking (p < 0.0001) and maternal periconceptional exposures (p < 0.0001), increasing CHD risk.

Conclusions:

  • The AhR p.Arg554Lys polymorphism is a risk factor for CHD in humans.
  • Parental exposures, particularly paternal smoking and maternal periconceptional exposures, interact with the AhR variant to exacerbate CHD risk.
  • These findings underscore the critical role of AhR in cardiovascular development and highlight gene-environment interactions in CHD etiology.
Keywords:
Aryl hydrocarbon receptorCongenital heart diseasePericonceptional exposurePolymorphism

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