Most Recent Award Year:
Lifestage of Participants:
Exposure: Prenatal; Adulthood (mother)
Air Pollutants: Tobacco smoke
Metabolic Outcomes: Obesity/body weight
Blood (mother); Cord blood; Saliva/buccal cells
Other Participant Data:
Questionnaire on sociodemographic data, smoking of cigarettes and other substances, dietary supplementation, use of assisted reproduction, and medical management during pregnancy obtained via medical records form (which can also be shared). Detailed parturition data were obtained including dose, duration and type of anesthesia used.
Genes or Other DNA Products Studied:
Developed assays to measuring methylation using pyrosequencing and measured it in ~400 cord blood DNA samples.
Epigenetic Mechanisms Studied:
DNA Methylation and gene expression
Loss of Imprinting in IGF2 has been found in a wide spectrum of adult chronic diseases including diabetes, cardiovascular diseases and malignancies. IGF2 imprint disorders have also been reported in patients with the human overgrowth disorder Beckwith-Wiedemann syndrome. Patients with Wilm's tumor and hepatoblastoma have a higher prevalence of LOI in IGF2. Methylation changes of differentially methylated regions on exon 3 and 9 of IGF2 have also been reported in lymphocytes of patients with colon cancer and leukemia. Factors underlying these epigenetic alterations are unknown, although environmental exposures such as cigarette smoking have been implicated. The timing of this epigenetic event is also unknown, although accumulating evidence suggests that LOI in IGF2 may occur in-utero. We hypothesize that LOI in IGF2 is a response, in part, to aberrant methylation changes in IGF2, and because these methylation patterns are mitotically heritable, contributes to deleterious outcomes inherent in IGF2 deregulation. The specific aims of the study are: 1) To characterize methylation patterns and estimate the prevalence of LOI in IGF2 in-utero; 2) To evaluate whether maternal exposure to cigarette smoking is associated with LOI in IGF2; and 3) To evaluate whether LOI in IGF2 is associated with rapid infant weight gain during the first year of life, characteristic of infants of smoking mothers. The proposed research builds on an existing data collection structure of the Cord Blood Transplantation (COBLT) Project. This project recruits and stores cord blood of participants from all Obstetrics Care facilities in Durham, Orange and Wake Counties. We will prospectively identify 200 smoking and 200 non-smoking mothers from the Project database and obtain up to 5ml of cord blood at delivery to determine IGF2 DNA methylation patterns and biallelic expression of IGF2. We will then examine these patterns according to maternal smoking status and infant weight gain. Because LOI is potentially reversible with imprinting restored since the DMA sequence remains unaltered, (unless mutation is in genes regulating methylation) identifying the timing of IGF2 LOI and factors influencing this epigenetic event has wide ranging intervention prospects on clinically apparent chronic disease incidence. The proposed study also has the potential to provide a foundation for future studies investigating the etiology of chronic diseases, including diabetes, cardiovascular diseases and some cancers. ExpandCollapse Abstract
Related NIEHS-Funded Study Populations
Newborn Epigenetics Study Cohort (NEST)
Hoyo, Cathrine; Murphy, Susan | Study Population Page Study Population c178
Durham, North Carolina
Number of Participants::
2,500 Mother-Infant Pairs
This is a birth cohort study investigating how early life environmental exposures and nutrition affect DNA methylation profiles in newborns. Infants were followed throughout early childhood to determine if methylation profiles established in utero are associated with childhood obesity and neurobehavioral outcomes. Since 2004, NEST has enrolled more than 2,500 women in central North Carolina.