Vitamin C Prevents Offspring DNA Methylation Changes Associated with Maternal Smoking in Pregnancy

Shorey‐Kendrick, Lyndsey E.; McEvoy, Cindy T.; Ferguson, Betsy; Burchard, Julja; Park, Byung; Gao, Lina; Vuylsteke, Brittany; Milner, Kristin; Morris, Cynthia D.; Spindel, Eliot R.

doi:10.1164/rccm.201610-2141oc

Cited by 81 publications

(36 citation statements)

References 48 publications

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“…Later in a supplementation trial, significant restoration was found of both genomic and tissue-specific methylation related to maternal smoking. More importantly, the restoration was associated with lung function in newborns [ 91 ]. Colostrum omega-3 PUFAs levels were found to be associated with mean FEV 1 and FEV 1 /FVC ratio at 12 years in a high-risk birth cohort [ 92 ].…”

Section: Dietary Intervention In Early Lifementioning

confidence: 99%

Potential Micronutrients and Phytochemicals against the Pathogenesis of Chronic Obstructive Pulmonary Disease and Lung Cancer

Zhai

et al. 2018

Nutrients

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Lung cancer and chronic obstructive pulmonary disease have shared etiology, including key etiological changes (e.g., DNA damage and epigenetics change) and lung function impairment. Focusing on those shared targets may help in the prevention of both. Certain micronutrients (vitamins and minerals) and phytochemicals (carotenoids and phenols) have potent antioxidant or methyl-donating properties and thus have received considerable interest. We reviewed recent papers probing into the potential of nutrients with respect to lung function preservation and prevention of lung cancer risk, and suggest several hypothetical intervention patterns. Intakes of vitamins (i.e., A, C, D, E, B12), carotenoids, flavonoids, curcumins, resveratrol, magnesium, and omega-3 fatty acids all show protective effects against lung function loss, some mainly by improving average lung function and others through reducing decline rate. Dietary interventions early in life may help lung function reserve over the lifespan. Protective nutrient interventions among smokers are likely to mitigate the effects of cigarettes on lung health. We also discuss their underlying mechanisms and some possible causes for the inconsistent results in observational studies and supplementation trials. The role of the lung microbiome on lung health and its potential utility in identifying protective nutrients are discussed as well. More prospective cohorts and well-designed clinical trials are needed to promote the transition of individualized nutrient interventions into health policy.

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Section: Dietary Intervention In Early Lifementioning

confidence: 99%

Potential Micronutrients and Phytochemicals against the Pathogenesis of Chronic Obstructive Pulmonary Disease and Lung Cancer

Zhai

et al. 2018

Nutrients

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“…Given that a high proportion of smokers are unable to quit during pregnancy even with cessation counseling, it is critical to identify modifiable factors that may mitigate the adverse effects of maternal smoking on child health. A recent study suggested that nutritional factors may partly modify the influence of maternal smoking during pregnancy on the newborn epigenome [32]. Folate is critical to fetal growth and development because it is an important component in the one-carbon metabolism pathway and provides methyl groups for a range of biochemical reactions, including DNAm [33].…”

Section: Introductionmentioning

confidence: 99%

Maternal smoking during pregnancy and cord blood DNA methylation: new insight on sex differences and effect modification by maternal folate levels

Zhang

Hong

et al. 2018

Epigenetics

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Maternal smoking during pregnancy may affect newborn DNA methylation (DNAm). However, little is known about how these associations vary by a newborn's sex and/or maternal nutrition. To fill in this research gap, we investigated epigenome-wide DNAm associations with maternal smoking during pregnancy in African American mother-newborn pairs. DNAm profiling in cord (n = 379) and maternal blood (n = 300) were performed using the Illumina HumanMethylation450 BeadChip array. We identified 12 CpG sites whose DNAm levels in cord blood were associated with maternal smoking, at a false discovery rate <5%. The identified associations in the GFI1 gene were more pronounced in male newborns than in females (P = 0.002 for maternal smoking × sex interaction at cg18146737). We further observed that maternal smoking and folate level may interactively affect cord blood DNAm level at cg05575921 in the AHRR gene (P = 5.0 × 10 for interaction): compared to newborns unexposed to maternal smoking and with a high maternal folate level (>19.2 nmol/L), the DNAm level was about 0.03 lower (P = 3.6 × 10) in exposed newborns with a high maternal folate level, but was 0.08 lower (P = 1.2 × 10) in exposed newborns with a low maternal folate level. Our data suggest that adequate maternal folate levels may partly counteract the impact of maternal smoking on DNAm. These findings may open new avenues of inquiry regarding sex differences in response to environmental insults and novel strategies to mitigate their intergenerational health effects through optimization of maternal nutrition.

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“…Epigenetic programming may be involved in the consequences of PTS on offspring health outcomes. PTS is now clearly linked to alterations in newborn DNA methylation patterns in multiple tissues, which may persist into childhood and even adolescence and are further linked to adverse fetal and childhood health outcomes [ 9 , 43 – 46 ]. Given AXL ’s key role in innate immune inflammation and lung homeostasis pathways [ 13 – 15 , 47 ], it stands to reason that a systemic alteration to AXL regulation during fetal development by an exposure such as tobacco smoke might negatively impact function of all tissues and cells in which AXL has an active role.…”

Section: Discussionmentioning

confidence: 99%

Self-reported prenatal tobacco smoke exposure, AXL gene-body methylation, and childhood asthma phenotypes

et al. 2018

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BackgroundEpigenetic 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.MethodsWe 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.ResultsPTS 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.ConclusionsPTS was associated with methylation level of AXL and the combination altered the risk of childhood bronchitic symptoms.Electronic supplementary materialThe online version of this article (10.1186/s13148-018-0532-x) contains supplementary material, which is available to authorized users.

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Vitamin C Prevents Offspring DNA Methylation Changes Associated with Maternal Smoking in Pregnancy

Cited by 81 publications

References 48 publications

Potential Micronutrients and Phytochemicals against the Pathogenesis of Chronic Obstructive Pulmonary Disease and Lung Cancer

Potential Micronutrients and Phytochemicals against the Pathogenesis of Chronic Obstructive Pulmonary Disease and Lung Cancer

Maternal smoking during pregnancy and cord blood DNA methylation: new insight on sex differences and effect modification by maternal folate levels

Self-reported prenatal tobacco smoke exposure, AXL gene-body methylation, and childhood asthma phenotypes

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