BACKGROUND: Mutations of the melanocortin-4 receptor (MC4R) gene are associated with up to 5.8% of monogenetic causes of obesity. Correlations between defects in MC4R and complications after laparoscopic adjustable gastric banding (LAGB) have recently been reported. The aim of this study was to investigate whether in our patient population band-associated complications can be correlated with MC4R defects, which in turn could be a contraindication for gastric banding. METHODS: Of 370 morbidly obese patients operated between Dec 1996 and May 2004 with LAGB, 37 required re-operation, by re-banding or biliopancreatic diversion/duodenal switch for band-associated complications. Genomic DNA was extracted from leucocytes of these 37 patients using standard methods. The entire MC4R-gene was amplified by PCR and sequenced on an ABI Prism 3100 automated DNA sequencer. Any detected mutation or polymorphism was verified utilizing a high-fidelity proofreading polymerase. RESULTS: No mutation was seen in 35 patients (95%). The polymorphism Ile251Leu (A1144C) which was found in one patient is known not to be associated with obesity. A silent mutation Ile198Ile (C594T) was found in another patient. Based on published data, approximately 12 patients of the 37 would have been expected to carry one of the known obesity-associated MC4R mutations, but none of these was found. CONCLUSION: In our patient material, we could not confirm the observation previously published that MC4R defects are associated with a higher complication rate following LAGB. Thus, we do not recommend routine general screening for MC4R defects before LAGB.
BACKGROUND: Mutations of the melanocortin-4 receptor (MC4R) gene are associated with up to 5.8% of monogenetic causes of obesity. Correlations between defects in MC4R and complications after laparoscopic adjustable gastric banding (LAGB) have recently been reported. The aim of this study was to investigate whether in our patient population band-associated complications can be correlated with MC4R defects, which in turn could be a contraindication for gastric banding. METHODS: Of 370 morbidly obesepatients operated between Dec 1996 and May 2004 with LAGB, 37 required re-operation, by re-banding or biliopancreatic diversion/duodenal switch for band-associated complications. Genomic DNA was extracted from leucocytes of these 37 patients using standard methods. The entire MC4R-gene was amplified by PCR and sequenced on an ABI Prism 3100 automated DNA sequencer. Any detected mutation or polymorphism was verified utilizing a high-fidelity proofreading polymerase. RESULTS: No mutation was seen in 35 patients (95%). The polymorphism Ile251Leu (A1144C) which was found in one patient is known not to be associated with obesity. A silent mutation Ile198Ile (C594T) was found in another patient. Based on published data, approximately 12 patients of the 37 would have been expected to carry one of the known obesity-associated MC4R mutations, but none of these was found. CONCLUSION: In our patient material, we could not confirm the observation previously published that MC4R defects are associated with a higher complication rate following LAGB. Thus, we do not recommend routine general screening for MC4R defects before LAGB.
Authors: Margaret A Stefater; Hilary E Wilson-Pérez; Adam P Chambers; Darleen A Sandoval; Randy J Seeley Journal: Endocr Rev Date: 2012-05-01 Impact factor: 19.871
Authors: Uyenlinh L Mirshahi; Christopher D Still; Kathryn K Masker; Glenn S Gerhard; David J Carey; Tooraj Mirshahi Journal: J Clin Endocrinol Metab Date: 2011-10-05 Impact factor: 5.958