Department of Pediatrics, Chonnam National University Hospital, Chonnam National University Medical School, Gwangju, Korea.
Asan Medical Center, Asan Institute for Life Sciences, Environmental Health Center, Seoul, Korea.
Yonsei Med J. 2020 Feb;61(2):186-191. doi: 10.3349/ymj.2020.61.2.186.
An outbreak of fatal humidifier disinfectant lung injuries (HDLI) occurred in Korea. Human studies on mechanisms underlying HDLI have yet to be conducted. This study aimed to investigate methylation changes and their potential role in HDLI after exposure to HDs containing polyhexamethylene guanidine-phosphate. DNA methylation analysis was performed in blood samples from 10 children with HDLI and 10 healthy children using Infinium Human MethylationEPIC BeadChip. Transcriptome analysis was performed using lung tissues from 5 children with HDLI and 5 controls. Compared to healthy controls, 92 hypo-methylated and 79 hyper-methylated CpG sites were identified in children with HDLI at the statistical significance level of |Δβ|>0.2 and <0.05. NOTCH1 was identified as a candidate network hub gene in cases. NOTCH1 transcripts significantly increased in lung tissues from HDLI cases compared to unexposed controls (=0.05). NOTCH1 may play an important role in pulmonary fibrosis of HDLI.
韩国发生了致命加湿器消毒剂肺病（HDLI）疫情。目前尚未对 HDLI 的发病机制进行人体研究。本研究旨在探讨暴露于含聚六亚甲基胍-磷酸盐的 HD 后，甲基化变化及其在 HDLI 中的潜在作用。使用 Infinium Human MethylationEPIC BeadChip，对 10 名 HDLI 患儿和 10 名健康儿童的血液样本进行了 DNA 甲基化分析。对 5 名 HDLI 患儿和 5 名对照的肺组织进行了转录组分析。与健康对照组相比，HDLI 患儿有 92 个低甲基化和 79 个高甲基化 CpG 位点，|Δβ|>0.2 和 <0.05。NOTCH1 被鉴定为病例中候选网络枢纽基因。与未暴露对照相比，HDLI 病例的肺组织中 NOTCH1 转录本显著增加（=0.05）。NOTCH1 可能在 HDLI 的肺纤维化中发挥重要作用。
