title: Eating Behavior, Low-Frequency Functional Mutations in the Melanocortin-4 Receptor (MC4R) Gene, and Outcomes of Bariatric Operations: A 6-Year Prospective Study.
abstract: Data on the effects of eating behavior and genetics on outcomes of gastrointestinal surgery for diabesity have been sparse, often flawed, and controversial. We aimed to assess long-term outcomes of bariatric operations in patients characterized for eating behavior and rare mutations in the melanocortin-4 receptor (MC4R) gene, which is strongly implicated in energy balance.
  
  
  
  Between 1996 and 2005, 1,264 severely obese Swiss patients underwent current laparoscopic adjustable gastric banding, gastroduodenal bypass, or a hybrid operation. Of these, 872 patients were followed for a minimum of 6 years and were screened for MC4R mutations. Using regression models, we studied relationships between eating behavior and MC4R mutations and postoperative weight loss, complications, and reoperations after 6 years.
  
  
  
  At baseline, rare functional MC4R mutation carriers exhibited a significantly higher prevalence of binge eating disorder (BED) or loss-of-control eating independent of age, sex, and BMI. Six years after bariatric surgery, the mutation carriers had more major complications than wild-type subjects independent of age, baseline BMI, sex, operation type, and weight loss. Furthermore, high baseline BMI, male sex, BED, and functional MC4R mutations were independent predictors of higher reoperation rates.
  
  
  
  Sequencing of MC4R and eating typology, combined with stratification for sex and baseline BMI, might significantly improve patient allocation to banding or bypass operations for diabesity as well as reduce both complication and reoperation rates.
authors.affiliation: CNRS UMR 8199, Lille Pasteur Institute, Lille, France Lille University, Lille, France European Genome Institute for Diabetes, FR 3508, Lille, France Department of Genomics of Common Disease, School of Public Health, Hammersmith Hospital, Imperial College London, London, U.K.
authors.forename: Amélie
authors.initials: A
authors.lastname: Bonnefond
authors.affiliation: Department of Internal Medicine, Landesspital Liechtenstein, Vaduz, Liechtenstein Dr. Horber Adipositas Stiftung, Zurich, Switzerland.
authors.forename: Ramsi
authors.initials: R
authors.lastname: Keller
authors.affiliation: Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: David
authors.initials: D
authors.lastname: Meyre
authors.affiliation: CNRS UMR 8199, Lille Pasteur Institute, Lille, France Lille University, Lille, France European Genome Institute for Diabetes, FR 3508, Lille, France.
authors.forename: Fanny
authors.initials: F
authors.lastname: Stutzmann
authors.affiliation: CNRS UMR 8199, Lille Pasteur Institute, Lille, France Lille University, Lille, France European Genome Institute for Diabetes, FR 3508, Lille, France.
authors.forename: Dorothée
authors.initials: D
authors.lastname: Thuillier
authors.affiliation: Scientific Computing Center and Departments of Surgery, Medicine, and Cell Biology, SUNY Downstate Medical Center, Brooklyn, NY.
authors.forename: Dimitre G
authors.initials: DG
authors.lastname: Stefanov
authors.affiliation: CNRS UMR 8199, Lille Pasteur Institute, Lille, France Lille University, Lille, France European Genome Institute for Diabetes, FR 3508, Lille, France Department of Genomics of Common Disease, School of Public Health, Hammersmith Hospital, Imperial College London, London, U.K. froguel@good.ibl.fr fritz.horber@landesspital.li jkral@downstate.edu.
authors.forename: Philippe
authors.initials: P
authors.lastname: Froguel
authors.affiliation: Department of Internal Medicine, Landesspital Liechtenstein, Vaduz, Liechtenstein Dr. Horber Adipositas Stiftung, Zurich, Switzerland University of Bern, Bern, Switzerland froguel@good.ibl.fr fritz.horber@landesspital.li jkral@downstate.edu.
authors.forename: Fritz F
authors.initials: FF
authors.lastname: Horber
authors.affiliation: Scientific Computing Center and Departments of Surgery, Medicine, and Cell Biology, SUNY Downstate Medical Center, Brooklyn, NY froguel@good.ibl.fr fritz.horber@landesspital.li jkral@downstate.edu.
authors.forename: John G
authors.initials: JG
authors.lastname: Kral
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D050110:Bariatric Surgery / Q000009:adverse effects*; D056912:Binge-Eating Disorder / Q000209:etiology / Q000235:genetics*; D015992:Body Mass Index; D005247:Feeding Behavior; D005260:Female; D005500:Follow-Up Studies; D005786:Gene Expression Regulation; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009765:Obesity / Q000601:surgery*; D011446:Prospective Studies; D044105:Receptor, Melanocortin, Type 4 / Q000235:genetics*; D017422:Sequence Analysis, DNA; D015431:Weight Loss / Q000235:genetics; D055815:Young Adult
chemical_list: C470072:MC4R protein, human; D044105:Receptor, Melanocortin, Type 4