Prenatal Tobacco Smoke Exposure Affects Global and Gene-specific DNA Methylation

Abstract

Rationale: Prenatal exposure to tobacco smoke increases the risk for diseases later in the child's life that may be mediated through alterations in DNA methylation. Objectives: To demonstrate that differences in DNA methylation patterns occur in children exposed to tobacco smoke and that variation in detoxification genes may alter these associations. Methods: Methylation of DNA repetitive elements, LINE1 and AluYb8, was measured using bisulfite conversion and pyrosequencing in buccal cells of 348 children participating in the Children's Health Study. Gene-specific CpG methylation differences associated with smoke exposure were screened in 272 participants in the Children's Health Study children using an Illumina GoldenGate panel. CpG loci that demonstrated a statistically significant difference in methylation were validated by pyrosequencing. Estimates were standardized across loci using a Z score to enable crosscomparison of results. Measurements and Main Results: DNA methylation patterns were associated with in utero exposure to maternal smoking. Exposed children had significantly lower methylation of AluYb8 (b, 20.31; P 5 0.03). Differences in smoking-related effects on LINE1 methylation were observed in children with the common GSTM1 null genotype. Differential methylation of CpG loci in eight genes was identified through the screen. Two genes, AXL and PTPRO, were validated by pyrosequencing and showed significant increases in methylation of 0.37 (P 5 0.005) and 0.34 (P 5 0.02) in exposed children. The associations with maternal smoking varied by a common GSTP1 haplotype. Conclusions: Life-long effects of in utero exposures may be mediated through alterations in DNA methylation. Variants in detoxification genes may modulate the effects of in utero exposure through epigenetic mechanisms.

Gestational intake of methyl donors and global LINE-1 DNA methylation in maternal and cord blood: Prospective results from a folate-replete population

“…However, we used the most technologically advanced and validated methods currently available for LINE-1 methylation analysis and have already demonstrated a relationship between higher LINE-1 and male sex and several other obesity-related risk factors in offspring in early life. 17 This method for LINE-1 methylation analysis has been shown in previous investigations to be sensitive to environmental and host-related factors, including age, 18 sex, 16,19 smoking 20 and tobacco smoke components, 21 physical activity 22 and environmental pollution. [23][24][25][26] Also, we measured DNA methylation only in blood DNA and we cannot exclude that methylation changes due to dietary components might be present in other tissues in the same individuals.…”

Neonatal DNA methylation profile in human twins is specified by a complex interplay between intrauterine environmental and genetic factors, subject to tissue-specific influence

“…This does not rule out the possibility that a minority of genes are influenced by a common environment. Indeed, previous genome-scale studies of DNA methylation have found a range of probes significantly associated with maternal environmental, from 0.6% (Breton et al 2009) and 1.1% (Fryer et al 2011) to 23% (Katari et al 2009). Because the accuracy of the estimation of effect size depends on study power, further investigation in larger numbers of twins is needed (Visscher 2004).…”

No Correlation between Beta2-Adrenergic Receptor Polymorphisms and the Severity and Clinical Control of Geriatric Asthma and COPD

“…Additionally, we did not assess second hand smoke exposure in our patient population. Environmental exposures such as smoking or second hand smoking are known epigenetic modifiers via DNA methylation [34][35]. Epigenetic changes can additionally be affected by diet and aging [36][37].…”