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
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
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DOI：
10.1016/j.envint.2018.08.046
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发表时间：
2018-12-01
影响因子：
11.8
通讯作者：
Kishi, Reiko
中科院分区：
文献类型：
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作者：
Bamai, Yu Ait;Araki, Atsuko;Kishi, Reiko
背景和目的：接触邻苯二甲酸盐和磷阻燃剂 (PFR) 被认为是哮喘和过敏的危险因素。然而，人们对编码丝聚蛋白（FLG）基因的功能丧失突变对这些关联的影响知之甚少，FLG被认为是湿疹和哮喘的诱发因素。我们调查了日本儿童接触灰尘中的邻苯二甲酸盐和 PFR 与湿疹/喘息之间的关联，同时考虑到 FLG 的功能丧失突变。方法：本研究是北海道环境与儿童健康研究的一部分。采用气相色谱质谱法测定了家庭灰尘中的 7 种邻苯二甲酸盐和 11 种 PFR。使用国际儿童哮喘和过敏研究调查问卷对 7 岁儿童的湿疹和喘息进行评估。之前在日本人群中发现的八种 FLG 突变是从脐带血样本中提取的。具有一种或多种 FLG 突变的儿童被认为是 FLG 突变阳性。该研究纳入了 296 名拥有完整数据（出生记录、FLG 突变、妊娠早期和 7 岁调查问卷以及邻苯二甲酸盐/PFR 水平）的儿童。通过逻辑回归计算对数转换的邻苯二甲酸盐/PFR 水平的湿疹和喘息的比值比 (OR) 和 95% 置信区间 (CI)。我们还根据FLG突变进行了分层分析。结果：湿疹和喘息的患病率分别为20.6%和13.9%。在没有任何 FLG 突变的儿童中，磷酸鸢尾 (1, 3-二氯-2-丙基) (TDCIPP) 增加了喘息的 OR（OR：1.22，CI：1.00-1.48）。在没有任何 FLG 突变的儿童中，磷酸（2-丁氧基乙基）酯 (TBOEP) 与湿疹之间以及邻苯二甲酸二异壬酯 (DiNP) 与湿疹之间的趋势分别存在显着的 p 值。 结论：尽管我们的样本量和横断面研究设计有限，但室内环境因素对儿童湿疹和喘息的影响在没有 FLG 功能丧失突变的儿童中比在儿童中更明显。 有突变的儿童。患有 FLG 突变的儿童可能已经在药物或父母生活方式方面得到了不同的照顾。有必要在更大的人群中进行进一步的研究，以便调查症状的严重程度和 FLG 突变的组合。
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, Iris (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 Iris (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.