Endoscopic Findings in Patients with Melanocortin-4 Receptor Gene Variants

Abstract

Background: Melanocortin-4 receptor gene (MC4R) variants, common in monogenic obesity, are associated with binge eating disorder (BED), which in turn may be associated with esophagogastric pathology. Adjustable gastric banding (AGB) may also affect foregut physiology. The effects of BED and/or MC4R variants on the foregut before and after AGB are not known. Methods: The complete coding region of MC4R was comparatively sequenced in 300 patients (233 women; age 42±1 years [mean±SEM]; BMI 43.5±0.3 kg/m2) having AGB. BED was determined in a semi-structured interview using the Spitzer Questionnaire. Findings on endoscopy and esophagram were compared in patients with and without gene variants and with and without BED before and a mean 36+3 months after AGB. Results: 6.3% of patients carried MC4R variants. All MC4R variant carriers had BED, compared to 18.1% of non-carriers (P<0.001). BED was associated with more oesophageal erosions before surgery (53.8% vs. 28.2%, p=0.015) and higher rate of persistence of oesophagitis (34.6% vs. 13.3%, p=0.017) and more gastritis after 3 years (15.4% vs. 3.9%, p=0.048). In contrast, postoperatively MC4R variant carriers had dilated oesophagi (2.5cm vs. 1.3cm, P<0.001), more vomiting (vomiting score 1.47±0.21 vs. 1.12±0.06, P<0.05 and five-fold more gastric complications (P<0.001) than non-carriers. Conclusion: BED is associated with esophagogastric lesions in obese patients, whereas MC4R may independently influence gastrointestinal motility.