ORIGINALRESEARCH
Maternal pre-pregnancy BMI downregulates neonatal cord blood LEP methylation R. Kadakia1,2, Y. Zheng3,4, Z. Zhang3,5, W. Zhang3,6, L. Hou3,6† and J. L. Josefson1,2†
1
Division of Endocrinology, Ann and Robert H. Lurie Childrenˈs Hospital of Chicago, Chicago, IL, USA; 2 Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, IL, USA; 3 Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA; 4 Health Sciences Integrated PhD Program, Northwestern University Feinberg School of Medicine, Chicago, IL, USA; 5 Driskill Graduate Program in Life Sciences, Northwestern University Feinberg School of Medicine, Chicago, IL, USA; 6 Robert H. Lurie Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL, USA †Drs. Hou and Josefson contributed
Summary Background: Neonatal adiposity has many determinants and may be a risk factor for future obesity. Epigenetic regulation of metabolically important genes is a potential contributor. Objectives: The objective of the study is to determine whether methylation changes in the LEP gene in cord blood DNA are impacted by the maternal environment or affect neonatal adiposity measures. Methods: A cross-sectional study of 114 full-term neonates born to healthy mothers with normal glucose tolerance was performed. Cord blood was assayed for leptin and genome-wide DNA methylation profiles via the Illumina 450K platform. Neonatal body composition was measured by air displacement plethysmography. Multivariate linear regression models and semi-partial correlation coefficients were used to analyze associations. False discovery rate was estimated to account for multiple comparisons.
equally as senior authors. Address for correspondence: R Kadakia, MD, Division of Endocrinology, Ann and Robert H. Lurie Childrenˈs Hospital of Chicago and Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. E-mail:
[email protected] Received 9 May 2016; revised 2 September 2016; accepted 28 October 2016
Results: Maternal pre-pregnancy BMI was associated with decreased methylation at five CpG sites near the LEP transcription start site in an adjusted model (false discovery rate
