Department of Environmental and Occupational Health, College of Medicine, National Cheng Kung University, Cheng-Hsing Campus, No. 1, University Road, Tainan City, Taiwan.
Research Center of Environmental Trace Toxic Substances, National Cheng Kung University, Tainan, Taiwan.
Clin Epigenetics. 2021 Apr 9;13(1):76. doi: 10.1186/s13148-021-01061-1.
Dysregulation of thymic stromal lymphopoietin (TSLP) expressions is linked to asthma and allergic disease. Exposure to phthalate esters, a widely used plasticizer, is associated with respiratory and allergic morbidity. Dibutyl phthalate (DBP) causes TSLP upregulation in the skin. In addition, phthalate exposure is associated with changes in environmentally induced DNA methylation, which might cause phenotypic heterogeneity. This study examined the DNA methylation of the TSLP gene to determine the potential mechanism between phthalate exposure and allergic diseases.
Among all evaluated, only benzyl butyl phthalate (BBzP) in the settled dusts were negatively correlated with the methylation levels of TSLP and positively associated with children's respiratory symptoms. The results revealed that every unit increase in BBzP concentration in the settled dust was associated with a 1.75% decrease in the methylation level on upstream 775 bp from the transcription start site (TSS) of TSLP (β = - 1.75, p = 0.015) after adjustment for child's sex, age, BMI, parents' smoking status, allergic history, and education levels, PM, formaldehyde, temperature; and relative humidity. Moreover, every percentage increase in the methylation level was associated with a 20% decrease in the risk of morning respiratory symptoms in the children (OR 0.80, 95% CI 0.65-0.99).
Exposure to BBzP in settled dust might increase children's respiratory symptoms in the morning through decreasing TSLP methylation. Therefore, the exposure to BBzP should be reduced especially for the children already having allergic diseases.
胸腺基质淋巴细胞生成素 (TSLP) 表达失调与哮喘和过敏性疾病有关。邻苯二甲酸酯类物质作为一种广泛使用的增塑剂，其暴露与呼吸道和过敏性发病率有关。邻苯二甲酸二丁酯 (DBP) 可导致皮肤 TSLP 上调。此外，邻苯二甲酸酯类物质的暴露与环境诱导的 DNA 甲基化变化有关，这种变化可能导致表型异质性。本研究检测了 TSLP 基因的 DNA 甲基化，以确定邻苯二甲酸酯类物质暴露与过敏性疾病之间的潜在机制。
在所评估的所有物质中，仅居室内尘埃中的苯二甲酸丁基苄基酯 (BBzP) 与 TSLP 的甲基化水平呈负相关，与儿童的呼吸道症状呈正相关。结果表明，居室内尘埃中 BBzP 浓度每增加一个单位，TSLP 转录起始位点 (TSS) 上游 775 bp 的甲基化水平就会降低 1.75%（β=-1.75，p=0.015），校正儿童的性别、年龄、BMI、父母吸烟状况、过敏史和教育水平、PM、甲醛、温度和相对湿度后。此外，甲基化水平每增加一个百分点，儿童患清晨呼吸道症状的风险就会降低 20%（OR 0.80，95%CI 0.65-0.99）。
居室内尘埃中 BBzP 的暴露可能通过降低 TSLP 甲基化来增加儿童清晨的呼吸道症状。因此，应减少 BBzP 的暴露，特别是对于已经患有过敏性疾病的儿童。
