Editors' ChoiceEpigenetics

Smoking Moms and Methylation

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Science Translational Medicine  18 Dec 2013:
Vol. 5, Issue 216, pp. 216ec207
DOI: 10.1126/scitranslmed.3008133

Since the 1970s when it was first proposed, the developmental origins of adult health hypothesis has gained momentum. The idea that the in utero environment influences health later in life is being confirmed by numerous epidemiological and experimental studies. The main mechanism driving these influences appears to be of epigenetic origin, in which genes are modified without altering the DNA sequence. Smoking during pregnancy is thought to create an in utero environment that is detrimental to the future health of the fetus, but data that describe the mechanistic underpinnings are scarce. Now, Maccani and colleagues begin to fill in these knowledge gaps by comparing the epigenetic status of placentas from smoker and nonsmoker mothers and the relationship of epigenetic changes to the gestational age of the fetus.

The authors used Human Methylation27 BeadChip technology to examine the methylation status of 21,551 autosomal CpG loci and found that 1918 of the loci in multiple genes had differential methylation-status patterns associated with maternal smoking. They then focused on characterizing methylation patterns of specific loci within the RUNX3 gene. This gene is known to be significantly associated with airway hyperresponsiveness and asthma, which in turn are associated with maternal smoking during pregnancy. Methylation values in seven RUNX3 loci were significantly associated with maternal smoking; two of these were associated with decreased gestational age, and one with increased risk for preterm birth.

A major limitation of the study is the use of the Methylation27 platform to assess methylation status. Repeating the same study with the Methylation450 array platform should yield considerably more information about the developmental origins of adult disease, specifically asthma and airway hyperresponsiveness.

J. Z. Maccani et al., Placental DNA methylation alterations associated with maternal tobacco smoking at the RUNX3 gene are also associated with gestational age. Epigenomics 5, 619–630 (2013). [Abstract]

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