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.
To determine the prevalence of genetic obesity in a large bariatric cohort and evaluate their response to bariatric surgery.
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).
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.
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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We would like to thank all participating patients for their contribution.
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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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
- Bariatric surgery
- Obesity genetics
- Gastric bypass
- Sleeve gastrectomy
- Revisional surgery
- Early onset obesity