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 HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Feng, N.
Right arrow Articles by Yanovski, J. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Feng, N.
Right arrow Articles by Yanovski, J. A.
Social Bookmarking
Add to CiteULike   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Diabetes 54:2663-2667, 2005
© 2005 by the American Diabetes Association, Inc.

Brief Genetics Reports

Co-occurrence of Two Partially Inactivating Polymorphisms of MC3R Is Associated With Pediatric-Onset Obesity

Ningping Feng1, Sharla F. Young2, Greti Aguilera2, Elena Puricelli1,3, Diane C. Adler-Wailes1, Nancy G. Sebring4, and Jack A. Yanovski1

1 Unit on Growth and Obesity, National Institutes of Health, Bethesda, Maryland
2 Section on Endocrine Physiology, Developmental Endocrinology Branch, National Institute of Child Health and Development, Rockville, Maryland
3 Pediatric Department, University of Insubria, Varese, Italy
4 Nutrition Department, Warren Grant Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland

Both human linkage studies and MC3R knockout mouse models suggest that the MC3R may play an important role in energy homeostasis. Here we show that among 355 overweight and nonoverweight children, 8.2% were double homozygous for a pair of missense MC3R sequence variants (Thr6Lys and Val81Ile). Such children were significantly heavier (BMI and BMI SD score: P < 0.0001), had more body fat (body fat mass and percentage fat mass: P < 0.001), and had greater plasma leptin (P < 0.0001) and insulin concentrations (P < 0.001) and greater insulin resistance (P < 0.008) than wild-type or heterozygous children. Both sequence variants were more common in African-American than Caucasian children. In vitro expression studies found the double mutant MC3R was partially inactive, with significantly fewer receptor binding sites, decreased signal transduction, and less protein expression. We conclude that diminished MC3R expression in this double MC3R variant may be a predisposing factor for excessive body weight gain in children.

Address correspondence and reprint requests to Jack A. Yanovski, MD, PhD, Unit on Growth and Obesity, National Institutes of Health, 10 Center Dr., Hatfield CRC, Rm 1-3330, MSC 1103, Bethesda, MD 20892-1862. E-mail: jy15i{at}nih.gov

Abbreviations: DMEM, Dulbecco’s modified Eagle’s medium; EGFP, enhanced green fluorescence protein; FACS, fluorescence-assisted cell sorting; MSH, melanocyte-stimulating hormone; NDP {alpha}-MSH, (Nle4,D-Phe7) {alpha}-melanocyte-stimulating hormone


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?


This article has been cited by other articles:


Home page
 DiabetesHome page
Y. Seng Lee, L. Kok Seng Poh, B. Lay Kee Kek, and K. Yin Loke
The Role of Melanocortin 3 Receptor Gene in Childhood Obesity
Diabetes, October 1, 2007; 56(10): 2622 - 2630.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Clin. Nutr.Home page
N. Santoro, L. Perrone, G. Cirillo, P. Raimondo, A. Amato, C. Brienza, and E. M. del Giudice
Effect of the melanocortin-3 receptor C17A and G241A variants on weight loss in childhood obesity
Am. J. Clinical Nutrition, April 1, 2007; 85(4): 950 - 953.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
J. Rutanen, J. Pihlajamaki, M. Vanttinen, U. Salmenniemi, E. Ruotsalainen, T. Kuulasmaa, S. Kainulainen, and M. Laakso
Single Nucleotide Polymorphisms of the Melanocortin-3 Receptor Gene Are Associated with Substrate Oxidation and First-Phase Insulin Secretion in Offspring of Type 2 Diabetic Subjects
J. Clin. Endocrinol. Metab., March 1, 2007; 92(3): 1112 - 1117.
[Abstract] [Full Text] [PDF]

Home page
 Endocr. Rev.Home page
K. E. Foster-Schubert and D. E. Cummings
Emerging Therapeutic Strategies for Obesity
Endocr. Rev., December 1, 2006; 27(7): 779 - 793.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
Y. C. L. Tung, S. J. Piper, D. Yeung, S. O'Rahilly, and A. P. Coll
A Comparative Study of the Central Effects of Specific Proopiomelancortin (POMC)-Derived Melanocortin Peptides on Food Intake and Body Weight in Pomc Null Mice
Endocrinology, December 1, 2006; 147(12): 5940 - 5947.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
G. M. Sutton, J. L. Trevaskis, M. W. Hulver, R. P. McMillan, N. J. Markward, M. J. Babin, E. A. Meyer, and A. A. Butler
Diet-Genotype Interactions in the Development of the Obese, Insulin-Resistant Phenotype of C57BL/6J Mice Lacking Melanocortin-3 or -4 Receptors
Endocrinology, May 1, 2006; 147(5): 2183 - 2196.
[Abstract] [Full Text] [PDF]


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