Abstract
Bariatric surgery is the most effective long term weight-loss therapy for severe and morbidly obese patients. Melanocortin-4 Receptor (MC4R) mutations, the most frequent known cause of monogenic obesity, affect the regulation of energy homeostasis. The impact of such mutations on weight loss after bariatric surgery is still debated.The objective is to determine the impact of MC4R status on weight loss in obese subjects over one year after bariatric surgery.A total of 648 patients, who were referred to bariatric surgery in a single clinical nutrition department, were genotyped for their MC4R status. The following four groups were categorized: functional MC4R mutations, MC4R single nucleotide polymorphisms (SNPs): Val103Ile (V103L) and Ile251Leu (I251L), MC4R variant rs17782313 (downstream of MC4R) and MC4R SNP A-178C on the promoter. Each patient was matched with two randomly paired controls without mutation. Matching factors were age, sex, baseline weight and type of surgery procedure (Roux-en-Y gastric bypass and adjustable gastric banding). We compared weight loss between cases and controls at 3, 6 and 12 months after surgery.Among 648 patients, we identified 9 carriers of functional MC4R mutations, 10 carriers of MC4R V103L and I251L SNPs, 7 carriers of the rs17792313 variant and 22 carriers of the A-178C SNP. Weight loss at 3, 6 and 12 months did not differ between cases and controls, whatever the MC4R mutations.This is the first case-control study to show that MC4R mutations and polymorphisms do not affect weight loss and body composition over one year after bariatric surgery.
Highlights
Obesity is a rapidly growing global public health challenge [1]
Melanocortin-4 Receptor (MC4R) genotyping Among the 648 patients screened for MC4R mutations, 9 were heterozygous for functional MC4R mutations, 10 heterozygous for MC4R single nucleotide polymorphisms (SNPs) V103L and I251L, 22 were heterozygous for the SNP A-178C located on the MC4R promoter and 7 carriers (4 heterozygous and 3 homozygous) of the variant rs17782313 located downstream of MC4R
At 6 months of follow-up, weight was significantly higher for polymorphism A-178C carriers (96.6614.4 kg) compared to non-carrier (92.4610.8 kg), but this difference disappeared 12 months after surgery
Summary
Obesity is a rapidly growing global public health challenge [1]. It is directly related to an increased risk for type 2 diabetes, hypertension, dyslipidemia, cardiovascular disease and overall mortality [2]. Bariatric surgery is the most effective therapy for long-term weight lost in severe or morbidly obese subjects [3,4]. Its use has dramatically increased during the last decade [1]. The individual weight loss response varies widely. Clinical and genetic factors may influence its effect. Genetic background accounts for 40% to 70% of an individual predisposition to obesity [5] with strong determinants of weight loss following bariatric surgery [6]
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