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Vol. 78, No. 4, 2012
Issue release date: November 2012
Section title: Original Paper
Horm Res Paediatr 2012;78:237–246
(DOI:10.1159/000343816)

Clinical and Functional Relevance of Melanocortin-4 Receptor Variants in Obese German Children

Melchior C. · Schulz A. · Windholz J. · Kiess W. · Schöneberg T. · Körner A.
aMolecular Biochemistry, Institute of Biochemistry and bCenter for Pediatric Research, University Hospital for Children and Adolescents, Medical Faculty, University of Leipzig, and cIFB Adiposity Diseases, Leipzig University Medical Center, Leipzig, Germany

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Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: 2/16/2012 1:38:55 PM
Accepted: 9/14/2012
Published online: 11/5/2012

Number of Print Pages: 10
Number of Figures: 2
Number of Tables: 2

ISSN: 1663-2818 (Print)
eISSN: 1663-2826 (Online)

For additional information: http://www.karger.com/HRP

Abstract

Background: Variants in the melanocortin-4 receptor (MC4R) gene are the most frequent cause of monogenic obesity. The relevance of MC4R variations with respect to clinical phenotype and biochemical function remains controversial. Methods: We sequenced the MC4R gene in 510 overweight/obese children. The clinical phenotype was assessed in a case-control setting matched for age, gender, puberty and body mass index. Identified MC4R variants were functionally characterized in vitro. Results: The frequency of MC4R variants was 5.3%, with functionally relevant mutations (D90N, V103I/S127L, R165W, G181D) occurring in 1.2% (confidence interval 0.26–2.15) of our sample. 4.1% were carriers of variants (Y35Y, V103I, T112M, M200V, I251L) with preserved receptor function in vitro. We did not detect large heterozygous deletions by multiple-ligand probe amplification assay. There were no differences in anthropometric or metabolic parameters between children with loss-of-function mutations and noncarriers. Carriers of the V103I or I251L variant had higher high-density lipoprotein cholesterol and HbA1c levels than matched noncarriers of MC4R variants. Conclusions: In our data set of childhood obesity in central Germany, we identified functionally relevant mutations in the MC4R gene in only 1.2% of the children. There were no major significant phenotypic differences between obese children with and without MC4R mutations. Hence, the diagnosis of genetically caused obesity due to MC4R mutation should be made with caution.


Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: 2/16/2012 1:38:55 PM
Accepted: 9/14/2012
Published online: 11/5/2012

Number of Print Pages: 10
Number of Figures: 2
Number of Tables: 2

ISSN: 1663-2818 (Print)
eISSN: 1663-2826 (Online)

For additional information: http://www.karger.com/HRP


Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
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