Diabetes
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Bell, C. G.
Right arrow Articles by Walley, A. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Bell, C. G.
Right arrow Articles by Walley, A. J.
Social Bookmarking
Add to CiteULike   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Diabetes 54:3049-3055, 2005
© 2005 by the American Diabetes Association, Inc.

Brief Genetics Reports

Association of Melanin-Concentrating Hormone Receptor 1 5' Polymorphism With Early-Onset Extreme Obesity

Christopher G. Bell1,2, David Meyre3, Chantal Samson3, Cliona Boyle1, Cécile Lecoeur3, Maïte Tauber4, Béatrice Jouret4, Delphine Jaquet5, Claire Levy-Marchal5, Marie Aline Charles6, Jacques Weill7, Fernando Gibson1, Charles A. Mein8, Philippe Froguel1,3, and Andrew J. Walley1

1 Section of Genomic Medicine, Faculty of Medicine, Imperial College, Hammersmith Hospital, London, U.K
2 Department of Haematology and Genetics, South Eastern Area Laboratory Services, Prince of Wales Hospital, Sydney, Australia
3 Centre National de la Recherche Scientifique, UMR 8090, Pasteur Institute, Lille, France
4 INSERM U563, Children’s Hospital, Toulouse, France
5 INSERM U457, Robert Debre Hospital, Paris, France
6 INSERM, U258-IFR69, Paris South Faculty of Medicine, Villejuif, France
7 Pediatric Endocrine Unit, Jeanne de Flandre Hospital, Lille, France
8 Bart’s and the London Genome Centre, Queen Mary’s School of Medicine, London, U.K

Murine models have been highly effective in identifying the monogenic forms of human obesity discovered to date. Melanin-concentrating hormone receptor 1 (MCHR1) has been shown to be significant in the downstream orexigenic activity of the leptin-melanocortin pathway by such models. In this study, the human MCHR1 gene was extensively characterized by sequencing 3.5 kb of coding, untranslated and intronic regions plus 1 kb of putative promoter region in 180 morbidly obese adults and 87 morbidly obese children, a total of >2.4 Mb of sequencing. Thirty-nine single nucleotide polymorphisms (SNPs) were found, seven of which encode an amino acid change. One mutation, R248Q, appeared to cosegregate with the obesity trait in one pedigree but was also found to be a rare polymorphism in control samples. To investigate the possible polygenic role of MCHR1, the six common SNPs (minor allele frequency >5%) found in the sequenced regions were then screened in 557 morbidly obese adults, 552 obese children, and 1,195 nonobese nondiabetic control subjects. The plausible promoter SNP, rs133068, was found to be associated with protection against obesity in obese children only (allele frequency P = 0.006 and genotype frequency P = 0.004). Most significant results were found when using a dominant model (P = 0.001, odds ratio 0.695 [95% CI 0.560–0.863]). However, similar associations were found when both adults and children were analyzed together (P = 0.006, 0.783 [0.658–0.930]), suggesting that severe forms of obesity with early onset may be associated with SNPs in MCHR1.

Address correspondence and reprint requests to Prof. Philippe Froguel, Section of Genomic Medicine, Faculty of Medicine, Imperial College, Hammersmith Hospital, Du Cane Rd., London, W12 0NN, U.K. E-mail: p.froguel{at}imperial.ac.uk

Abbreviations: MAF, minor allele frequency; MC4R, melanocortin 4 receptor; MCH, melanin-concentrating hormone; MCHR1, melanin-concentrating hormone receptor 1; SNP, single nucleotide polymorphism


Add to CiteULike CiteULike   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?




HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Diabetes Diabetes Care Clinical Diabetes Diabetes Spectrum
Copyright © 2005 by the American Diabetes Association.