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This article is part of the Research Topic

Epigenetic Regulations in Immune-Related Disorders

Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Genet. | doi: 10.3389/fgene.2019.00471

Paternal tobacco smoke correlated to offspring asthma and prenatal epigenetic programming

 Chih Chiang Wu1, 2*, Te-Yao Hsu3, Jen-Chieh Chang3, Chia-Yu Ou4,  Ho-Chang Kuo5, Chieh-An Liu1, Chih-Lu Wang1, Hau Chuang3, Chie-Pein Chen6 and  Kuender D. Yang6, 7*
  • 1Department of Pediatrics, Po-Zen Hospital, Taiwan
  • 2Institute of Clinical Medicine, National Yang-Ming University, Taiwan
  • 3Kaohsiung Chang Gung Memorial Hospital, Taiwan
  • 4Department of Obstetrics, Po-Zen Hospital, Taiwan
  • 5Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital, Taiwan
  • 6Mackay Memorial Hospital, Taiwan
  • 7National Yang-Ming University, Taiwan

Rationale: Little is known about effects of paternal tobacco smoke (PTS) on the offspring’s asthma and its prenatal epigenetic programming.
Objective: To investigate whether PTS exposure was associated with the offspring’s asthma and correlated to epigenetic CG methylation of potential tobacco-related immune genes: LMO2, GSTM1 or/and IL-10 genes.
Measurements and Main Results:
In a birth cohort of 1629 newborns, we measured exposure rates of PTS (23%) and maternal tobacco smoke (MTS, 0.2%), cord blood DNA methylation, infant respiratory tract infection, childhood DNA methylation and childhood allergic diseases. Infants with prenatal PTS exposure had a significantly higher risk of asthma by age of 6 than those without (p=0.026). The PTS exposure doses at 0, <20 and ≧20 cigarettes per day were significantly associated with the trend of childhood asthma and the increase of LMO2-E148 (p=0.006), and IL10_P325 (p=0.008) CG methylation. The combination of higher CG methylation levels of LMO2_E148, IL10_P325 and GSTM1_P266 corresponded to the highest risk of asthma by 43.48%, compared to other combinations (16.67%-23.08%) in the 3-way multi-factor dimensionality reduction (MDR) analysis. The LMO2_P794 and GSTM1_P266 CG methylation levels at age 0 were significantly correlated to those at age of 6.
Conclusions: Prenatal PTS exposure increases CG methylation contents of immune genes, such as LMO2 and IL-10, which significantly retained from newborn stage to 6 years of age and correlated to development of childhood asthma. Modulation of the LMO2 and IL-10 CG methylation and/or their gene expression may provide a regimen for early prevention of PTS-associated childhood asthma.

Keywords: Paternal tobacco smoke, Asthma development, CG methylation, Lmo2, IL10

Received: 08 Feb 2019; Accepted: 01 May 2019.

Edited by:

Douglas M. Ruden, Wayne State University, United States

Reviewed by:

Janine M. LaSalle, University of California, Davis, United States
Hehuang Xie, Virginia Tech, United States  

Copyright: © 2019 Wu, Hsu, Chang, Ou, Kuo, Liu, Wang, Chuang, Chen and Yang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
MD. Chih Chiang Wu, Po-Zen Hospital, Department of Pediatrics, Kaohsiung, Taiwan, phachang@gmail.com
MD, PhD. Kuender D. Yang, Mackay Memorial Hospital, Taipei, Taipei County, Taiwan, yangkd.yeh@hotmail.com