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Genetic Obesity and Bariatric Surgery Outcome in 1014 Patients with Morbid Obesity

  • M.I. CooimanEmail author
  • L. Kleinendorst
  • E.O. Aarts
  • I.M.C. Janssen
  • H.K. Ploos van Amstel
  • A.I. Blakemore
  • E.J. Hazebroek
  • H.J. Meijers-Heijboer
  • B. van der Zwaag
  • F.J. Berends
  • M.M. van Haelst
Original Contributions

Abstract

Background

Mutations in the leptin-melanocortin pathway genes are known to cause monogenic obesity. The prevalence of these gene mutations and their effect on weight loss response after bariatric surgery are still largely unknown.

Objective

To determine the prevalence of genetic obesity in a large bariatric cohort and evaluate their response to bariatric surgery.

Methods

Mutation analysis of 52 obesity-associated genes. Patient inclusion criteria were a BMI > 50 kg/m2, an indication for revisional surgery or an early onset of obesity (< 10 years of age).

Results

A total of 1014 patients were included, of whom 30 (3%) were diagnosed with genetic obesity, caused by pathogenic heterozygous mutations in either MC4R, POMC, PCSK1, SIM1, or PTEN. The percentage total body weight loss (%TBWL) after Roux-en-Y gastric bypass (RYGB) surgery was not significantly different for patients with a mutation in MC4R, POMC, and PCSK1 compared with patients lacking a molecular diagnosis. Of the confirmed genetic obesity cases, only patients with MC4R mutations receiving a sleeve gastrectomy (SG) showed significantly lower %TBWL compared with patients lacking a molecular diagnosis, during 2 years of follow-up.

Conclusions

In this cohort of morbid obese bariatric patients, an estimated prevalence of monogenic obesity of 3% is reported. Among these patients, the clinical effects of heterozygous mutations in POMC and PCSK1 do not interfere with the effectiveness of most commonly performed bariatric procedures within the first 2 years of follow-up. Patients with MC4R mutations achieved superior weight loss after primary RYGB compared with SG.

Keywords

Obesity Bariatric surgery Obesity genetics Gastric bypass Sleeve gastrectomy Revisional surgery Early onset obesity 

Notes

Acknowledgments

We would like to thank all participating patients for their contribution.

Compliance with Ethical Standards

This study was approved by the national ethical committee and written informed consent was obtained from all participants included in this study.

Conflict of Interest

The authors declare that they have no conflict of interest.

Supplementary material

11695_2019_4184_MOESM1_ESM.docx (50 kb)
ESM 1 (DOCX 50 kb)

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • M.I. Cooiman
    • 1
    • 2
    Email author
  • L. Kleinendorst
    • 3
  • E.O. Aarts
    • 1
  • I.M.C. Janssen
    • 1
    • 4
  • H.K. Ploos van Amstel
    • 5
  • A.I. Blakemore
    • 6
    • 7
  • E.J. Hazebroek
    • 1
  • H.J. Meijers-Heijboer
    • 2
    • 3
  • B. van der Zwaag
    • 5
  • F.J. Berends
    • 1
  • M.M. van Haelst
    • 2
    • 3
  1. 1.Department of Bariatric SurgeryRijnstate Hospital Arnhem/VitalysArnhemthe Netherlands
  2. 2.Department of Clinical Genetics, Amsterdam UMCVrije Universiteit AmsterdamAmsterdamthe Netherlands
  3. 3.Department of Clinical Genetics, Amsterdam UMCUniversity of AmsterdamAmsterdamthe Netherlands
  4. 4.Department of SurgeryNederlandse Obesitas Kliniek WestThe HagueThe Netherlands
  5. 5.Department of GeneticsUniversity Medical Center UtrechtUtrechtthe Netherlands
  6. 6.Department of Life SciencesBrunel University LondonLondonUK
  7. 7.Section of Investigative MedicineImperial College LondonLondonUK

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