标题：Association of filaggrin gene mutations and childhood eczema and wheeze with phthalates and phosphorus flame retardants in house dust: The Hokkaido study on Environment and Children's Health
摘要：Background and aim: Exposure to phthalates and phosphorus flame retardants (PFRs) is considered to be a risk
factor for asthma and allergies. However, little is known about the contribution of loss-of-function mutations in
the gene encoding filaggrin (FLG) gene, which are considered to be predisposing factors for eczema and asthma,
to these associations. We investigated the associations between exposure to phthalates and PFRs in dust and
eczema/wheeze among Japanese children, taking into consideration loss-of-function mutations in FLG.
Methods: This study was part of the Hokkaido study on Environment and Children's Health. Seven phthalates
and 11 PFRs in household dust were measured by gas chromatography–mass spectrometry. Eczema and wheeze
were assessed in children aged 7 years using the International Study of Asthma and Allergies in Childhood
questionnaire. Eight FLG mutations previously identified in the Japanese population were extracted from cord
blood samples. Children with one or more FLG mutations were considered to be positive for FLG mutations. The
study included 296 children who had complete data (birth records, FLG mutations, first trimester and 7 years
questionnaires, and phthalate/PFR levels). Odds ratios (ORs) and 95% confidential intervals (CIs) of eczema and
wheeze were calculated for log-transformed phthalate/PFR levels by logistic regression. We also performed
stratified analyses based on FLG mutations.
Results: The prevalence rates of eczema and wheeze were 20.6% and 13.9%, respectively. Among children
without any FLG mutations, tris (1, 3-dichloro-2-propyl) phosphate (TDCIPP) increased the OR of wheeze, (OR:
1.22, CI: 1.00–1.48). Significant p values for trends were found between tris (2-butoxyethyl) phosphate (TBOEP)
and eczema and di-iso-nonyl phthalate (DiNP) and eczema among children without any FLG mutations, respectively.
Conclusions: Despite our limited sample size and cross-sectional study design, the effects of indoor environmental factors on childhood eczema and wheeze were clearer in children without loss-of-function mutations in
FLG than in children with mutations. Children with FLG mutations might already be cared for differently in
terms of medication or parental lifestyle. Further studies in larger populations are warranted so that severity of
symptoms and combinations of FLG mutations can be investigated.
