A child’s surroundings in the first couple of years of birth could influence the inherited risk of developing eczema, research suggests, with proximity to dogs particularly lessening the strength of one genetic variant.
The findings, published in Allergy, suggest that although people may be genetically predisposed to the dry, inflamed skin condition, exposure to certain environmental factors can increase or decrease this risk.
Altogether, seven factors including antibiotic use and having an elder sibling showed an interaction with genes predisposing to eczema, with exposure to dogs being particularly powerful.
The study is the largest and most comprehensive analysis to date investigating the interaction between genes and environment in atopic eczema, the investigators claim.
Researcher Sara Brown, PhD, from the University of Edinburgh, said the study aimed to answer some of the most difficult questions she was asked in clinic by caregivers, such as why a child had eczema and what could be done to help protect their baby.
“We know that genetic make-up affects a child’s risk of developing eczema and previous studies have shown that owning a pet dog may be protective, but this is the first study to show how this may occur at a molecular level,” she continued.
“More work is needed, but our findings mean we have a chance to intervene in the rise of allergic disease, to protect future generations.”
Atopic eczema, also known as atopic dermatitis, is a chronic inflammatory skin and systemic condition affecting approximately one in five children and one in ten adults living in high-income countries.
Although it is a heritable trait, its rapid rise in prevalence over the past 30 years in industrialized areas demonstrates the importance of environmental factors in its etiology.
Brown and co-workers used 16 studies to explore interactions between 24 most significant risk loci that have been associated with atopic eczema in genome-wide association studies and 18 early-life environmental factors.
Early-life environmental exposures consisting of those in utero and within the first 2 years of life were included to minimize reverse causation.
The team then tested the gene-environment interactions in an additional 10 studies of European populations and carried out in vitro modeling using a skin keratinocyte model to validate the identified interactions.
The initial analysis involved 25,339 people, suggesting evidence for interaction between at least one established genetic variant for eczema and seven environmental factors: antibiotic use; cat ownership; dog ownership; breastfeeding; elder sibling; smoking; and washing practices and at least one established genetic variant for eczema. In all, there were 14 interactions.
The following analysis of 254,532 people showed that exposure to dogs interacted with the rs10214237 variant on chromosome 5 and correlated with the expression of the interleukin-7 receptor, which is a protein involved in immune cell function.
Further investigation revealed that canine proximity impacted this genetic variant on eczema, providing a protective effect via the interleukin-7 receptor gene, and possibly also interleukin-10, by suppressing skin inflammation.
The authors add: “There may be an equivalent interaction effect with siblings, but this is not possible to model in vitro.”
They suggest that the effect of other interactions could be weak and may be unlikely to have important contributions to eczema pathogenesis.