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

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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.

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Acknowledgments

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

Author information

Authors and Affiliations

  1. Department of Bariatric Surgery, Rijnstate Hospital Arnhem/Vitalys, Wagnerlaan 55, 6815 AD, Arnhem, the Netherlands

    M.I. Cooiman, E.O. Aarts, I.M.C. Janssen, E.J. Hazebroek & F.J. Berends

  2. Department of Clinical Genetics, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands

    M.I. Cooiman, H.J. Meijers-Heijboer & M.M. van Haelst

  3. Department of Clinical Genetics, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands

    L. Kleinendorst, H.J. Meijers-Heijboer & M.M. van Haelst

  4. Department of Surgery, Nederlandse Obesitas Kliniek West, The Hague, The Netherlands

    I.M.C. Janssen

  5. Department of Genetics, University Medical Center Utrecht, Utrecht, the Netherlands

    H.K. Ploos van Amstel & B. van der Zwaag

  6. Department of Life Sciences, Brunel University London, London, UK

    A.I. Blakemore

  7. Section of Investigative Medicine, Imperial College London, London, UK

    A.I. Blakemore

Authors
  1. M.I. Cooiman
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  2. L. Kleinendorst
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  3. E.O. Aarts
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  4. I.M.C. Janssen
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  5. H.K. Ploos van Amstel
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  6. A.I. Blakemore
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  7. E.J. Hazebroek
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  8. H.J. Meijers-Heijboer
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  9. B. van der Zwaag
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  10. F.J. Berends
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  11. M.M. van Haelst
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Corresponding author

Correspondence to M.I. Cooiman.

Ethics declarations

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

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The authors declare that they have no conflict of interest.

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Cooiman, M., Kleinendorst, L., Aarts, E. et al. Genetic Obesity and Bariatric Surgery Outcome in 1014 Patients with Morbid Obesity. OBES SURG 30, 470–477 (2020). https://doi.org/10.1007/s11695-019-04184-w

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  • DOI: https://doi.org/10.1007/s11695-019-04184-w

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