Ten-eleven translocation 1 (TET1) methylation is associated with childhood asthma and traffic-related air pollution

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:137

Article

Somineni, Hari K.¹  Zhang, Xue²  Myers, Jocelyn M. Biagini¹  Kovacic, Melinda Butsch^1,3,5  Ulm, Ashley¹  Jurcak, Noelle⁴  Ryan, Patrick H.^3,5  Hershey, Gurjit K. Khurana¹  Ji, Hong¹ 

[1] Cincinnati Childrens Hosp Med Ctr, Div Asthma Res, 3333 Burnet Ave,MLC 7037, Cincinnati, OH 45229 USA

[2] Cincinnati Childrens Hosp Med Ctr, Div Human Genet, Cincinnati, OH 45229 USA

[3] Cincinnati Childrens Hosp Med Ctr, Div Biostat & Epidemiol, Cincinnati, OH 45229 USA

[4] Johns Hopkins Univ, Sch Med, Baltimore, MD USA

[5] Univ Cincinnati, Dept Environm Hlth, Cincinnati, OH 45221 USA

关键词: DNA methylation;    TET1;    5-hmC;    nasal epithelial cells;    cross-tissue marker;    traffic-related air pollution;    asthma;   

DOI  :  10.1016/j.jaci.2015.10.021

来源: Elsevier

【 摘 要 】

Background: Asthma is a complex disorder influenced by genetics and the environment. Recent findings have linked abnormal DNA methylation in T cells with asthma; however, the potential dysregulation of methylation in airway epithelial cells is unknown. Studies of mouse models of asthma have observed greater levels of 5-hydroxymethylcytosine (5-hmC) and ten-eleven translocation 1 (TET1) expression in lungs. TET proteins are known to catalyze methylation through modification of 5-methylcytosine to 5-hmC. Objective: We sought to examine the association of TET1 methylation with asthma and traffic-related air pollution (TRAP). Methods: TET1 methylation levels from DNA derived from nasal airway epithelial cells collected from 12 African American children with physician-diagnosed asthma and their nonasthmatic siblings were measured by using Illumina 450K arrays. Regions of interest were verified by means of locus-specific pyrosequencing in 35 sibling pairs and replicated in an independent population (n = 186). Exposure to TRAP in participants' early life and at current home addresses was estimated by using a land-use regression model. Methylation studies in saliva, PBMCs, and human bronchial epithelial cells were done to support our findings. Results: Loss of methylation at a single CpG site in the TET1 promoter (cg23602092) and increased global 5-hmC levels were significantly associated with asthma. In contrast, TRAP exposure at participants' current homes significantly increased methylation at the same site. Patterns were consistent across tissue sample types. 5-Aza-29-deoxycytidine and diesel exhaust particle exposure in human bronchial epithelial cells was associated with altered TET1 methylation and expression and global 5-hmC levels. Conclusions: Our findings suggest a possible role of TET1 methylation in asthmatic patients and response to TRAP.

【 授权许可】

Free