Atopic dermatitis in adolescents: Role of carbonyl reductase 3 genetic risk score under constant chronic exposure to particulate matter

The pathogenesis of atopic dermatitis (AD) involves an impairment of the skin barrier by an interplay of genetic and environmental factors, incl. particulate matter (PM). A gene that is upregulated in PM-exposed lung cells and correlates with inflammatory responses encodes carbonyl reductase 3 (CBR3). CBR3 is also inducible by air pollutants in keratinocytes, so we constructed aCBR3 genetic risk score (GRS) for AD under constant chronic PM exposure. We used data between birth and age 15 (years 2011–13) from 428 adolescents enrolled in the GINIplus/LISA study. AD at age 15 was defined as ever-diagnosed by a physician. Individual exposures to PMs with a median aerodynamic diameter of ≤2.5, ≤10, 2.5–10 μm (PM2.5, PM10, PMcoarse), and the reflectance of PM2.5 filters (PMabsorbance) were modeled within the ESCAPE project using land-use regression. Chronic exposures were estimated using the centered means of cumulative exposures to each PM over 15 years. Out of 52 CBR3 single nucleotide polymorphisms (SNPs), we constructed and evaluated a GRS utilizing bagging and random forests as the statistical learning procedure. The effect of the GRS on AD adjusted for the exposure to each PM separately and potential confounders were investigated by logistic regression. Our results showed significant effects of CBR3 GRS on AD under constant chronic exposure to each PM (AD diagnoses: 34.8%; PM2.5, PM10, PMabsorbance: p-value=0.009; PMcoarse: p-value=0.008). Furthermore, we identified 8 SNPs presenting the highest protective (rs881712, rs879892, rs12626189, rs9305578, rs1971504, rs2242803, and rs10470174) or risk (rs45622637) trends of CBR3 SNPs. In conclusion the individual susceptibility to AD in adolescents under constant chronic PM exposure is likely affected by CBR3 variations. A combination of epidemiological and mechanistic studies is required to gain further insights into the underlying pathophysiology.