203879 Global DNA hypomethylation in cord blood serum of babies exposed to maternal smoking in-utero

Wednesday, November 11, 2009: 11:21 AM

Rafael Guerrero-Preston, Dr PH, MPH , Otolaryngology Department, Johns Hopkins University, Baltimore, MD
Cynthia LeBron, PhD , Otolaryngology Department, Johns Hopkins University, Baltimore, MD
Marina Roystacher, MS , Surgical Oncology Laboratory, Department of Surgery, Hadassah Hebrew University Medical Center, Jerusalem, Israel
Julie B. Herbstman, ScM, PhD , Columbia Center for Children's Environmental Health, Columbia University Mailman School of Public Health, New York, NY
Rolf U. Halden, PhD , Center for Environmental Biotechnology, Arizona State University, Tempe, AZ
Frank R. Witter, MD , Dept. of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, MD
David Sidransky, MD , Otolaryngology Department, Johns Hopkins University, Baltimore, MD
Lynn Goldman, MD, MPH , Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD
  
Active smoking is known to be associated with global DNA hypomethylation in aerodigestive mucosa, but similar studies for in-utero exposed newborns are lacking. We hypothesized that maternal smoking also should be associated with global DNA hypomethylation in cord blood serum of full term babies with adequate birthweigth. We used an ELISA based kit (Sigma) to measure global DNA methylation in cord blood serum and in umbilical cord tissue of babies with high (mean = 171.4 ng/ml) and very low (mean = 0.09 ng/ml) serum cotinine levels.

The global DNA methylation level in cord blood serum was significantly lower (p<0.001) for five newborns exposed to maternal smoking, mean = 8.74 (95% CI, 1.5, 15.9), when compared to seven non-exposed newborns, mean = 25.5 (95% CI, 16.2, 34.8). The natural log of the serum cotinine levels were negatively correlated to the global DNA methylation levels in serum (r = -0.73, p<0.001) in a dose-response pattern. The global DNA methylation index in umbilical cord tissue was not significantly lower (p = 0.66) for newborns exposed to maternal smoking, mean = 33.4 (95% CI, 23.3, 43.5), when compared to non-exposed newborns, mean = 36.3 (95% CI, 23.8, 48.8).

These results suggest that circulating fetal DNA already exhibits aberrant methylation patterns. Global DNA hypomethylation is known to be associated with genomic fragility, aberrant gene expression and a series of chronic diseases, including diabetes, bipolar disorders, obesity, schizophrenia, and cancer. Therefore, these preliminary results point towards the need of strengthening smoking cessation efforts among pregnant women.

Learning Objectives:
1) Define global and gene specific DNA methylation 2) Describe the association between cigarette smoke and DNA methylation in cord blood serum 3) Assess the health risk associated to global DNA hypomethylation at birth.

Keywords: Child Health, Genetics

Presenting author's disclosure statement:

Qualified on the content I am responsible for because: I have been doing epigenetics research since 2006 and have published on DNA methylation as well as on children's health
Any relevant financial relationships? No

I agree to comply with the American Public Health Association Conflict of Interest and Commercial Support Guidelines, and to disclose to the participants any off-label or experimental uses of a commercial product or service discussed in my presentation.

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