title: Roux-en Y gastric bypass surgery induces genome-wide promoter-specific changes in DNA methylation in whole blood of obese patients.
abstract: BACKGROUND
  DNA methylation has been proposed to play a critical role in many cellular and biological processes.
  
  
  OBJECTIVE
  To examine the influence of Roux-en-Y gastric bypass (RYGB) surgery on genome-wide promoter-specific DNA methylation in obese patients. Promoters are involved in the initiation and regulation of gene transcription.
  
  
  METHODS
  Promoter-specific DNA methylation in whole blood was measured in 11 obese patients (presurgery BMI >35 kg/m(2), 4 females), both before and 6 months after RYGB surgery, as well as once only in a control group of 16 normal-weight men. In addition, body weight and fasting plasma glucose were measured after an overnight fast.
  
  
  RESULTS
  The mean genome-wide distance between promoter-specific DNA methylation of obese patients at six months after RYGB surgery and controls was shorter, as compared to that at baseline (p<0.001). Moreover, postsurgically, the DNA methylation of 51 promoters was significantly different from corresponding values that had been measured at baseline (28 upregulated and 23 downregulated, P<0.05 for all promoters, Bonferroni corrected). Among these promoters, an enrichment for genes involved in metabolic processes was found (n = 36, P<0.05). In addition, the mean DNA methylation of these 51 promoters was more similar after surgery to that of controls, than it had been at baseline (P<0.0001). When controlling for the RYGB surgery-induced drop in weight (-24% of respective baseline value) and fasting plasma glucose concentration (-16% of respective baseline value), the DNA methylation of only one out of 51 promoters (~2%) remained significantly different between the pre-and postsurgery time points.
  
  
  CONCLUSIONS
  Epigenetic modifications are proposed to play an important role in the development of and predisposition to metabolic diseases, including type II diabetes and obesity. Thus, our findings may form the basis for further investigations to unravel the molecular effects of gastric bypass surgery.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT01730742.
authors.affiliation: Department of Neuroscience, BMC, box 593, 75124 Uppsala, Sweden.
authors.forename: Emil K
authors.initials: EK
authors.lastname: Nilsson
authors.affiliation: Interdisciplinary Obesity Center, eSwiss Medical & Surgical Center, St. Gallen, Switzerland.
authors.forename: Barbara
authors.initials: B
authors.lastname: Ernst
authors.affiliation: Department of Neuroscience, BMC, box 593, 75124 Uppsala, Sweden.
authors.forename: Sarah
authors.initials: S
authors.lastname: Voisin
authors.affiliation: Department of Neuroscience, BMC, box 593, 75124 Uppsala, Sweden.
authors.forename: Markus Sällman
authors.initials: MS
authors.lastname: Almén
authors.affiliation: Department of Neuroscience, BMC, box 593, 75124 Uppsala, Sweden.
authors.forename: Christian
authors.initials: C
authors.lastname: Benedict
authors.affiliation: Department of Neuroscience, BMC, box 593, 75124 Uppsala, Sweden.
authors.forename: Jessica
authors.initials: J
authors.lastname: Mwinyi
authors.affiliation: Interdisciplinary Obesity Center, eSwiss Medical & Surgical Center, St. Gallen, Switzerland.
authors.forename: Robert
authors.initials: R
authors.lastname: Fredriksson
authors.affiliation: Interdisciplinary Obesity Center, eSwiss Medical & Surgical Center, St. Gallen, Switzerland.
authors.forename: Bernd
authors.initials: B
authors.lastname: Schultes
authors.affiliation: Department of Neuroscience, BMC, box 593, 75124 Uppsala, Sweden.
authors.forename: Helgi B
authors.initials: HB
authors.lastname: Schiöth
mesh_terms: D000328:Adult; D000713:Anastomosis, Roux-en-Y / Q000009:adverse effects*; D019175:DNA Methylation; D005260:Female; D015894:Genome, Human; D006801:Humans; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000235:genetics / Q000601:surgery*; D011401:Promoter Regions, Genetic