Melanocortin-4 receptor mutations and polymorphisms do not affect weight loss after bariatric surgery

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.

Figure 1. Weight loss over 12 months after bariatric surgery according to MC4R genotype (mean±SEM).

Weight loss was expressed as a percentage of weight at baseline (surgery). Carriers and non-carriers were matched for age, sex, weight and surgery procedure (gastric banding or bypass). A) Weight loss in carriers and non-carriers of functional MC4R mutations. B) Weight loss data in carriers and non-carriers of the allele rs17782313-C. C) Weight loss data in carriers and non-carriers of MC4R polymorphisms Ile251Leu, Val103Ile, D) Weight loss data in carriers and non-carriers of MC4R polymorphism A_178C.

Figure 2. Fat mass percentage at 12 months after bariatric surgery according to MC4R genotype.

A, plot percentage of fat mass in carriers and non-carriers of functional MC4R mutations. B, plot percentage of fat mass in carriers and non-carriers of the allele rs17782313-C. C, plot percentage of fat mass in carriers and non-carriers of MC4R polymorphisms: Ile251Leu, Val103Ile. D, plot percentage of fat mass in carriers and non-carriers of MC4R polymorphism: A_178C.