Differential methylation in glucoregulatory genes of offspring born before vs. after maternal gastrointestinal bypass surgery
- Frédéric Guénarda,
- Yves Deshaiesb,c,
- Katherine Cianfloneb,c,
- John G. Krald,
- Picard Marceauc,e, and
- Marie-Claude Vohla,1
- aInstitute of Nutrition and Functional Foods and Department of Food Science and Nutrition, and
- Departments of bMedicine and
- eSurgery, Laval University, Quebec City, QC G1V 0A6, Canada;
- cQuébec Heart and Lung Institute, Quebec City, QC G1V 4G5, Canada; and
- dDepartment of Surgery, State University of New York Downstate Medical Center, Brooklyn, NY 11203
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Edited by C. Ronald Kahn, Joslin Diabetes Center, Harvard Medical School, Boston, MA, and approved April 30, 2013 (received for review October 10, 2012)
Abstract
Obesity and overnutrition during pregnancy affect fetal programming of adult disease. Children born after maternal bariatric gastrointestinal bypass surgery (AMS) are less obese and exhibit improved cardiometabolic risk profiles carried into adulthood compared with siblings born before maternal surgery (BMS). This study was designed to analyze the impact of maternal weight loss surgery on methylation levels of genes involved in cardiometabolic pathways in BMS and AMS offspring. Differential methylation analysis between a sibling cohort of 25 BMS and 25 AMS (2–25 y-old) offspring from 20 mothers was conducted to identify biological functions and pathways potentially involved in the improved cardiometabolic profile found in AMS compared with BMS offspring. Links between gene methylation and expression levels were assessed by correlating genomic findings with plasma markers of insulin resistance (fasting insulin and homeostatic model of insulin resistance). A total of 5,698 genes were differentially methylated between BMS and AMS siblings, exhibiting a preponderance of glucoregulatory, inflammatory, and vascular disease genes. Statistically significant correlations between gene methylation levels and gene expression and plasma markers of insulin resistance were consistent with metabolic improvements in AMS offspring, reflected in genes involved in diabetes-related cardiometabolic pathways. This unique clinical study demonstrates that effective treatment of a maternal phenotype is durably detectable in the methylome and transcriptome of subsequent offspring.
Footnotes
- ↵1To whom correspondence should be addressed. E-mail: marie-claude.vohl{at}fsaa.ulaval.ca.
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Author contributions: Y.D., K.C., J.G.K., P.M., and M.-C.V. designed research; F.G., P.M., and M.-C.V. performed research; M.-C.V. contributed new reagents/analytic tools; F.G., J.G.K., P.M., and M.-C.V. analyzed data; and F.G., Y.D., K.C., J.G.K., P.M., and M.-C.V. wrote the paper.
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The authors declare no conflict of interest.
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This article is a PNAS Direct Submission.
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Data deposition: The data reported in this paper have been deposited in the Gene Expression Omnibus (GEO) database, www.ncbi.nlm.nih.gov/geo [accession nos. GSE44798 (gene methylation arrays) and GSE44407 (gene expression arrays)].
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This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1216959110/-/DCSupplemental.
