The University of Southampton
University of Southampton Institutional Repository

Association of melanin-concentrating hormone receptor 1 5' polymorphism with early-onset extreme obesity.

Association of melanin-concentrating hormone receptor 1 5' polymorphism with early-onset extreme obesity.
Association of melanin-concentrating hormone receptor 1 5' polymorphism with early-onset extreme obesity.
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.
0012-1797
3049-3055
Bell, Christopher
44982df7-0746-4cdb-bed1-0bdfe68f1a64
Meyre, David
023f567d-798c-41f0-a096-2028569a3976
Samson, Chantal
6c6af93b-5f91-4622-a29e-1cd16c37219a
Boyle, Cliona
b99cd2c8-3e00-4700-834a-6948c76b11d5
Lecoeur, Cécile
de08c41b-c24a-4ec3-82ef-c58a68a8ed34
Tauber, Maïte
d8ed1a1e-c7ff-45c8-a5eb-7d7907b07a96
Jouret, Béatrice
eca0273f-7417-4e83-a7bd-f0b621ae1348
Jaquet, Delphine
2ee05482-9fe7-44c5-94aa-29817356c44d
Levy-Marchal, Claire
2f09decb-6c29-4901-bf09-135c5691af34
Charles, Marie Aline
6258c9d7-9d1f-4717-abbf-23233e345946
Weill, Jacques
88b8cfe1-f76d-435f-a7a3-72cdb7d93c01
Gibson, Fernando
dd498592-b4e2-48bd-be9d-76ec6ece1a56
Mein, Charles A.
c1cc43af-6c34-47a4-a959-5105593bcbde
Froguel, Philippe
563ee961-98a3-4aed-98a5-d70e8350ef8c
Walley, Andrew J.
354e9819-2ef2-44ac-81dc-8068aa354c74
Bell, Christopher
44982df7-0746-4cdb-bed1-0bdfe68f1a64
Meyre, David
023f567d-798c-41f0-a096-2028569a3976
Samson, Chantal
6c6af93b-5f91-4622-a29e-1cd16c37219a
Boyle, Cliona
b99cd2c8-3e00-4700-834a-6948c76b11d5
Lecoeur, Cécile
de08c41b-c24a-4ec3-82ef-c58a68a8ed34
Tauber, Maïte
d8ed1a1e-c7ff-45c8-a5eb-7d7907b07a96
Jouret, Béatrice
eca0273f-7417-4e83-a7bd-f0b621ae1348
Jaquet, Delphine
2ee05482-9fe7-44c5-94aa-29817356c44d
Levy-Marchal, Claire
2f09decb-6c29-4901-bf09-135c5691af34
Charles, Marie Aline
6258c9d7-9d1f-4717-abbf-23233e345946
Weill, Jacques
88b8cfe1-f76d-435f-a7a3-72cdb7d93c01
Gibson, Fernando
dd498592-b4e2-48bd-be9d-76ec6ece1a56
Mein, Charles A.
c1cc43af-6c34-47a4-a959-5105593bcbde
Froguel, Philippe
563ee961-98a3-4aed-98a5-d70e8350ef8c
Walley, Andrew J.
354e9819-2ef2-44ac-81dc-8068aa354c74

Bell, Christopher, Meyre, David, Samson, Chantal, Boyle, Cliona, Lecoeur, Cécile, Tauber, Maïte, Jouret, Béatrice, Jaquet, Delphine, Levy-Marchal, Claire, Charles, Marie Aline, Weill, Jacques, Gibson, Fernando, Mein, Charles A., Froguel, Philippe and Walley, Andrew J. (2005) Association of melanin-concentrating hormone receptor 1 5' polymorphism with early-onset extreme obesity. Diabetes, 54 (10), 3049-3055. (doi:10.2337/diabetes.54.10.3049). (PMID:16186414)

Record type: Article

Abstract

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.

Text
bell_d_05_MCHR1.pdf - Version of Record
Restricted to Repository staff only
Request a copy

More information

Accepted/In Press date: 1 June 2005
Published date: October 2005
Organisations: Human Development & Health, Centre for Biological Sciences, MRC Life-Course Epidemiology Unit

Identifiers

Local EPrints ID: 400998
URI: http://eprints.soton.ac.uk/id/eprint/400998
ISSN: 0012-1797
PURE UUID: bc000975-1037-4c2f-9ac6-1fcfd20bc142
ORCID for Christopher Bell: ORCID iD orcid.org/0000-0003-4601-1242

Catalogue record

Date deposited: 03 Oct 2016 14:02
Last modified: 15 Mar 2024 02:36

Export record

Altmetrics

Contributors

Author: Christopher Bell ORCID iD
Author: David Meyre
Author: Chantal Samson
Author: Cliona Boyle
Author: Cécile Lecoeur
Author: Maïte Tauber
Author: Béatrice Jouret
Author: Delphine Jaquet
Author: Claire Levy-Marchal
Author: Marie Aline Charles
Author: Jacques Weill
Author: Fernando Gibson
Author: Charles A. Mein
Author: Philippe Froguel
Author: Andrew J. Walley

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×