Loss of Imprinting in IGF2 has been found in a wide spectrum of adult chronic diseases jncluding 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. ? ? ?
|House, John S; Mendez, Michelle; Maguire, Rachel L et al. (2018) Periconceptional Maternal Mediterranean Diet Is Associated With Favorable Offspring Behaviors and Altered CpG Methylation of Imprinted Genes. Front Cell Dev Biol 6:107|
|Schechter, Julia C; Fuemmeler, Bernard F; Hoyo, Cathrine et al. (2018) Impact of Smoking Ban on Passive Smoke Exposure in Pregnant Non-Smokers in the Southeastern United States. Int J Environ Res Public Health 15:|
|Felix, Janine F; Joubert, Bonnie R; Baccarelli, Andrea A et al. (2018) Cohort Profile: Pregnancy And Childhood Epigenetics (PACE) Consortium. Int J Epidemiol 47:22-23u|
|Joubert, Bonnie R; Felix, Janine F; Yousefi, Paul et al. (2016) DNA Methylation in Newborns and Maternal Smoking in Pregnancy: Genome-wide Consortium Meta-analysis. Am J Hum Genet 98:680-96|
|Fuemmeler, Bernard F; Lee, Chien-Ti; Soubry, Adelheid et al. (2016) DNA Methylation of Regulatory Regions of Imprinted Genes at Birth and Its Relation to Infant Temperament. Genet Epigenet 8:59-67|
|Fuemmeler, Bernard F; Wang, Lin; Iversen, Edwin S et al. (2016) Association between Prepregnancy Body Mass Index and Gestational Weight Gain with Size, Tempo, and Velocity of Infant Growth: Analysis of the Newborn Epigenetic Study Cohort. Child Obes 12:210-8|
|Soubry, A; Murphy, S K; Wang, F et al. (2015) Newborns of obese parents have altered DNA methylation patterns at imprinted genes. Int J Obes (Lond) 39:650-7|
|Vidal, Adriana C; Overcash, Francine; Murphy, Susan K et al. (2013) Associations between birth and one year anthropometric measurements and IGF2 and IGF2R genetic variants in African American and Caucasian American infants. J Pediatr Genet 2:|
|Liu, Ying; Hoyo, Cathrine; Murphy, Susan et al. (2013) DNA methylation at imprint regulatory regions in preterm birth and infection. Am J Obstet Gynecol 208:395.e1-7|
|Soubry, Adelheid; Schildkraut, Joellen M; Murtha, Amy et al. (2013) Paternal obesity is associated with IGF2 hypomethylation in newborns: results from a Newborn Epigenetics Study (NEST) cohort. BMC Med 11:29|
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