Self-reported prenatal tobacco smoke exposure, AXL gene-body methylation, and childhood asthma phenotypes
Abstract Background Epigenetic modifications, including DNA methylation, act as one potential mechanism underlying the detrimental effects associated with prenatal tobacco smoke (PTS) exposure. Methylation in a gene called AXL was previously reported to differ in response to PTS. Methods We investig...
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| Format: | Article |
| Language: | English |
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BMC
2018-07-01
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| Series: | Clinical Epigenetics |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13148-018-0532-x |
| _version_ | 1818159818641244160 |
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| author | Lu Gao Xiaochen Liu Joshua Millstein Kimberly D. Siegmund Louis Dubeau Rachel L. Maguire Junfeng (Jim) Zhang Bernard F. Fuemmeler Scott H. Kollins Cathrine Hoyo Susan K. Murphy Carrie V. Breton |
| author_facet | Lu Gao Xiaochen Liu Joshua Millstein Kimberly D. Siegmund Louis Dubeau Rachel L. Maguire Junfeng (Jim) Zhang Bernard F. Fuemmeler Scott H. Kollins Cathrine Hoyo Susan K. Murphy Carrie V. Breton |
| author_sort | Lu Gao |
| collection | DOAJ |
| description | Abstract Background Epigenetic modifications, including DNA methylation, act as one potential mechanism underlying the detrimental effects associated with prenatal tobacco smoke (PTS) exposure. Methylation in a gene called AXL was previously reported to differ in response to PTS. Methods We investigated the association between PTS and epigenetic changes in AXL and how this was related to childhood asthma phenotypes. We tested the association between PTS and DNA methylation at multiple CpG loci of AXL at birth using Pyrosequencing in two separate study populations, the Children’s Health Study (CHS, n = 799) and the Newborn Epigenetic Study (NEST, n = 592). Plasma cotinine concentration was used to validate findings with self-reported smoking status. The inter-relationships among AXL mRNA and miR-199a1 expression, PTS, and AXL methylation were examined. Lastly, we evaluated the joint effects of AXL methylation and PTS on the risk of asthma and related symptoms at age 10 years old. Results PTS was associated with higher methylation level in the AXL gene body in both CHS and NEST subjects. In the pooled analysis, exposed subjects had a 0.51% higher methylation level in this region compared to unexposed subjects (95% CI 0.29, 0.74; p < 0.0001). PTS was also associated with 21.2% lower expression of miR-199a1 (95% CI − 37.9, − 0.1; p = 0.05), a microRNA known to regulate AXL expression. Furthermore, the combination of higher AXL methylation and PTS exposure at birth increased the risk of recent episodes of bronchitic symptoms in childhood. Conclusions PTS was associated with methylation level of AXL and the combination altered the risk of childhood bronchitic symptoms. |
| first_indexed | 2024-12-11T15:52:02Z |
| format | Article |
| id | doaj.art-4a179f99abf14c6ea21c7571f8c92666 |
| institution | Directory Open Access Journal |
| issn | 1868-7075 1868-7083 |
| language | English |
| last_indexed | 2024-12-11T15:52:02Z |
| publishDate | 2018-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Clinical Epigenetics |
| spelling | doaj.art-4a179f99abf14c6ea21c7571f8c926662022-12-22T00:59:33ZengBMCClinical Epigenetics1868-70751868-70832018-07-0110111110.1186/s13148-018-0532-xSelf-reported prenatal tobacco smoke exposure, AXL gene-body methylation, and childhood asthma phenotypesLu Gao0Xiaochen Liu1Joshua Millstein2Kimberly D. Siegmund3Louis Dubeau4Rachel L. Maguire5Junfeng (Jim) Zhang6Bernard F. Fuemmeler7Scott H. Kollins8Cathrine Hoyo9Susan K. Murphy10Carrie V. Breton11Department of Preventive Medicine, USC Keck School of MedicineDepartment of Preventive Medicine, USC Keck School of MedicineDepartment of Preventive Medicine, USC Keck School of MedicineDepartment of Preventive Medicine, USC Keck School of MedicineDepartment of Preventive Medicine, USC Keck School of MedicineDepartment of Biological Sciences, Center for Human Health and the Environment, North Carolina State UniversityNicholas School of the Environment and Duke Global Health Institute, Duke UniversityDepartment of Health Behavior and Policy, Massey Cancer Center, Virginia Commonwealth UniversityDepartment of Psychiatry and Behavioral Sciences, Duke University Medical CenterDepartment of Biological Sciences, Center for Human Health and the Environment, North Carolina State UniversityDivision of Reproductive Sciences, Department of Obstetrics and Gynecology, Duke University School of MedicineDepartment of Preventive Medicine, USC Keck School of MedicineAbstract Background Epigenetic modifications, including DNA methylation, act as one potential mechanism underlying the detrimental effects associated with prenatal tobacco smoke (PTS) exposure. Methylation in a gene called AXL was previously reported to differ in response to PTS. Methods We investigated the association between PTS and epigenetic changes in AXL and how this was related to childhood asthma phenotypes. We tested the association between PTS and DNA methylation at multiple CpG loci of AXL at birth using Pyrosequencing in two separate study populations, the Children’s Health Study (CHS, n = 799) and the Newborn Epigenetic Study (NEST, n = 592). Plasma cotinine concentration was used to validate findings with self-reported smoking status. The inter-relationships among AXL mRNA and miR-199a1 expression, PTS, and AXL methylation were examined. Lastly, we evaluated the joint effects of AXL methylation and PTS on the risk of asthma and related symptoms at age 10 years old. Results PTS was associated with higher methylation level in the AXL gene body in both CHS and NEST subjects. In the pooled analysis, exposed subjects had a 0.51% higher methylation level in this region compared to unexposed subjects (95% CI 0.29, 0.74; p < 0.0001). PTS was also associated with 21.2% lower expression of miR-199a1 (95% CI − 37.9, − 0.1; p = 0.05), a microRNA known to regulate AXL expression. Furthermore, the combination of higher AXL methylation and PTS exposure at birth increased the risk of recent episodes of bronchitic symptoms in childhood. Conclusions PTS was associated with methylation level of AXL and the combination altered the risk of childhood bronchitic symptoms.http://link.springer.com/article/10.1186/s13148-018-0532-xMethylationEpigeneticsSmoke |
| spellingShingle | Lu Gao Xiaochen Liu Joshua Millstein Kimberly D. Siegmund Louis Dubeau Rachel L. Maguire Junfeng (Jim) Zhang Bernard F. Fuemmeler Scott H. Kollins Cathrine Hoyo Susan K. Murphy Carrie V. Breton Self-reported prenatal tobacco smoke exposure, AXL gene-body methylation, and childhood asthma phenotypes Clinical Epigenetics Methylation Epigenetics Smoke |
| title | Self-reported prenatal tobacco smoke exposure, AXL gene-body methylation, and childhood asthma phenotypes |
| title_full | Self-reported prenatal tobacco smoke exposure, AXL gene-body methylation, and childhood asthma phenotypes |
| title_fullStr | Self-reported prenatal tobacco smoke exposure, AXL gene-body methylation, and childhood asthma phenotypes |
| title_full_unstemmed | Self-reported prenatal tobacco smoke exposure, AXL gene-body methylation, and childhood asthma phenotypes |
| title_short | Self-reported prenatal tobacco smoke exposure, AXL gene-body methylation, and childhood asthma phenotypes |
| title_sort | self reported prenatal tobacco smoke exposure axl gene body methylation and childhood asthma phenotypes |
| topic | Methylation Epigenetics Smoke |
| url | http://link.springer.com/article/10.1186/s13148-018-0532-x |
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