AUTHOR=Wu Chih-Chiang , Hsu Te-Yao , Chang Jen-Chieh , Ou Chia-Yu , Kuo Ho-Chang , Liu Chieh-An , Wang Chih-Lu , Chuang Hau , Chen Chie-Pein , Yang Kuender D. 

TITLE=Paternal Tobacco Smoke Correlated to Offspring Asthma and Prenatal Epigenetic Programming

JOURNAL=Frontiers in Genetics

VOLUME=10

YEAR=2019

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2019.00471

DOI=10.3389/fgene.2019.00471

ISSN=1664-8021

ABSTRACT=<p><bold>Rationale:</bold> Little is known about effects of paternal tobacco smoke (PTS) on the offspring’s asthma and its prenatal epigenetic programming.</p><p><bold>Objective:</bold> To investigate whether PTS exposure was associated with the offspring’s asthma and correlated to epigenetic CG methylation of potential tobacco-related immune genes: <italic>LMO2, GSTM1</italic> or/and <italic>IL-10</italic> genes.</p><p><bold>Measurements and Main Results:</bold> In a birth cohort of 1,629 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 the age of 6 than those without (<italic>p</italic> = 0.026). The PTS exposure doses at 0, &lt;20, and ≧20 cigarettes per day were significantly associated with the trend of childhood asthma and the increase of <italic>LMO2-E148</italic> (<italic>p</italic> = 0.006), and <italic>IL10_P325</italic> (<italic>p</italic> = 0.008) <italic>CG</italic> methylation. The combination of higher CG methylation levels of <italic>LMO2_E148, IL10_P325</italic>, and <italic>GSTM1_P266</italic> 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 <italic>LMO2_P794</italic> and <italic>GSTM1_P266</italic> CG methylation levels at age 0 were significantly correlated to those at age of 6.</p><p><bold>Conclusions:</bold> Prenatal PTS exposure increases CG methylation contents of immune genes, such as <italic>LMO2</italic> and <italic>IL-10</italic>, which significantly retained from newborn stage to 6 years of age and correlated to development of childhood asthma. Modulation of the <italic>LMO2</italic> and <italic>IL-10</italic> CG methylation and/or their gene expression may provide a regimen for early prevention of PTS-associated childhood asthma.</p><p><bold>Descriptor number:</bold> 1.10 Asthma Mediators.</p><p><bold>Scientific Knowledge on the Subject</bold>: It has been better known that maternal tobacco smoke (MTS) has an impact on the offspring’s asthma <italic>via</italic> epigenetic modification. Little is known about effects of paternal tobacco smoke (PTS) on the offspring’s asthma and its prenatal epigenetic programming.</p><p><bold>What This Study Adds to the Field</bold>: Prenatal tobacco smoke (PTS) can program epigenetic modifications in certain genes, such as <italic>LMO2</italic> and <italic>IL-10</italic>, and that these modifications are correlated to childhood asthma development. The higher the PTS exposure dose the higher the CG methylation levels are found. The combination of higher CG methylation levels of <italic>LMO2_E148, IL10_P325</italic> and <italic>GSTM1_P266</italic> corresponded to the highest risk of asthma. Measuring the DNA methylation levels of certain genes might help to predict high-risk populations for childhood asthma and provide a potential target to prevent the development of childhood asthma.</p>