Title page for ETD etd-11262009-175918


Document Type Master's Dissertation
Author Logan, Murray Glen
URN etd-11262009-175918
Document Title Investigation of MC4 receptor polymorphisms and the effect of bariatric surgery on a selected group of South African obese patients
Degree MSc
Department Immunology
Supervisor
Advisor Name Title
Prof T van der Merwe Co-Supervisor
Prof M Pepper Supervisor
Keywords
  • bariatric surgery
  • MC4 receptor polymorphisms
  • obese patients
Date 2009-09-02
Availability unrestricted
Abstract
A) Bariatric surgery for the treatment of obesity has shown much promise. The Roux-en-Y gastric bypass is a procedure that combines both restrictive and malabsorptive elements. Post-operative weight loss and co-morbidity improvements previously achieved are over and above those which are seen during life style modification and drug therapy. 330 patients (2005-2007) with a mean BMI of 45.87 ± 0.63 were characterised pre-operatively with regard to clinical, anthropometric and DEXA scan measurements. 130 were matched for the same parameters post-operatively over a 9-12 month observation period. The data was analysed statistically using paired t-tests and regression analyses. Significant post-operative improvements were observed with regard to patients’ weight loss and co-morbidity improvement. Positive and significant correlations of anthropometric measures to biochemical parameters ensued. Risk factor scoring methodology produced an average total score of 17 points / 36. Average post-op weight loss at 9-12 months follow-up was 20% of initial pre-op weight. Co-morbid diseases and anthropometric measurements illustrated significant changes following surgery. Risk factor scoring is a valuable pre-op tool for assessing eligibility for medical aid re-imbursement for surgery.

B) Obesity is a global epidemic and is increasing the worlds’ mortality rate. Genetic predisposition to obesity is recognized as being significant. Polymorphisms within the Melanocortin 4 Receptor (MC4R) gene, which encodes a G-protein coupled receptor responsible for post-prandial satiety signalling, have been associated with monogenic obesity. Obesity prevalence in South Africa is drastically increasing, however there has been no causative investigation done. Thus we sought to perform an initial assessment of the prevalence of MC4R polymorphisms within a South African representative group. Blood was drawn from a mixed Body Mass Index (BMI) cohort of 259 adult individuals and their DNA was extracted. The MC4R gene was PCR amplified from the DNA, the amplicon sequenced and the sequence data was analyzed for polymorphisms. A polymorphism prevalence of 13.51% was found within the patients across a BMI range that spanned from underweight (19.6) to super-obese (126.0). In addition to MC4R polymorphisms that had been identified previously, two new polymorphisms namely R7H and S36T were observed. Four haplotypes were also identified. MC4R mutation frequency was observed to be ethnically dependant; however the hypothesis of differing ethnic backgrounds illustrating varying mutational penetrance was not confirmed. The expected trend regarding MC4R polymorphism functional effect and associated pathogenicity was not followed in light of our results. The question of whether or not MC4R polymorphisms contribute to the development of obesity is indisputable; however the current accepted trend regarding their precise role may be incorrect and must be challenged.

© 2008, University of Pretoria. All rights reserved. The copyright in this work vests in the University of Pretoria. No part of this work may be reproduced or transmitted in any form or by any means, without the prior written permission of the University of Pretoria.

Please cite as follows:

Logan, MG 2008, Investigation of MC4 receptor polymorphisms and the effect of bariatric surgery on a selected group of South African obese patients , MSc dissertation, University of Pretoria, Pretoria, viewed yymmdd < http://upetd.up.ac.za/thesis/available/etd-11262009-175918/ >

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