Human Molecular Genetics, Vol 6, 675-679, Copyright © 1997 by Oxford University Press
DB Thompson, E Ravussin, PH Bennett and C Bogardus
The cloning of human and mouse cDNAs from brain that encode high affinity
leptin receptors was recently reported. We have physically localized the
human leptin receptor gene (LEPR) to a region at 1p31, between the
anonymous microsatellite markers D1S515 and D1S198. The genomic structure
of the human leptin receptor gene, corresponding to the published human
brain cDNA sequence, spans over 70 kb and includes 20 exons. Since the
leptin receptor gene is a candidate gene for obesity, and because of its
proximity to D1S198, a marker previously linked to insulin secretion, the
LEPR gene was sequenced in 20 non- diabetic Pima Indians chosen for
extremes in percent body fat and in their acute insulin response to
intravenous glucose. Seven polymorphic sites were identified. Two of these
polymorphisms, Lys109Arg and Gln223Arg, are amino acid substitutions in the
extracellular domain of the leptin receptor, one polymorphism is a silent
substitution, and four occur in non-coding regions of the leptin receptor.
Four of these sites are in linkage disequilibrium with one another.
Nucleotides at three noncoding polymorphic sites were found exclusively in
obese Pima Indians. This demonstrates an association between variation at
the leptin receptor gene and obesity in humans.
ARTICLES
Structure and sequence variation at the human leptin receptor gene in lean and obese Pima Indians
Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, AZ 85016, USA. bthompson@phx.niddk.nih.gov
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  M. Hanaoka, X. Yu, K. Urushihata, M. Ota, K. Fujimoto, and K. Kubo Leptin and Leptin Receptor Gene Polymorphisms in Obstructive Sleep Apnea Syndrome Chest, January 1, 2008; 133(1): 79 - 85. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Crabbe, S. Goemaere, H. Zmierczak, I. Van Pottelbergh, D. De Bacquer, and J.-M. Kaufman Are serum leptin and the Gln223Arg polymorphism of the leptin receptor determinants of bone homeostasis in elderly men? Eur. J. Endocrinol., May 1, 2006; 154(5): 707 - 714. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Paracchini, P. Pedotti, and E. Taioli Genetics of Leptin and Obesity: A HuGE Review Am. J. Epidemiol., July 15, 2005; 162(2): 101 - 114. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y.-J. Liu, S. M.S. Rocha-Sanchez, P.-Y. Liu, J.-R. Long, Y. Lu, L. Elze, R. R. Recker, and H.-W. Deng Tests of linkage and/or association of the LEPR gene polymorphisms with obesity phenotypes in Caucasian nuclear families Physiol Genomics, April 13, 2004; 17(2): 101 - 106. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. P. Cleary, S. C. Juneja, F. C. Phillips, X. Hu, J. P. Grande, and N. J. Maihle Leptin Receptor-Deficient MMTV-TGF-{alpha}/LeprdbLeprdb Female Mice Do Not Develop Oncogene-Induced Mammary Tumors Experimental Biology and Medicine, February 1, 2004; 229(2): 182 - 193. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Yiannakouris, M. Yannakoulia, L. Melistas, J. L. Chan, D. Klimis-Zacas, and C. S. Mantzoros The Q223R Polymorphism of the Leptin Receptor Gene Is Significantly Associated with Obesity and Predicts a Small Percentage of Body Weight and Body Composition Variability J. Clin. Endocrinol. Metab., September 1, 2001; 86(9): 4434 - 4439. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Wauters, I. Mertens, T. Rankinen, M. Chagnon, C. Bouchard, and L. Van Gaal Leptin Receptor Gene Polymorphisms Are Associated with Insulin in Obese Women with Impaired Glucose Tolerance J. Clin. Endocrinol. Metab., July 1, 2001; 86(7): 3227 - 3232. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Rosmond, Y. C. Chagnon, G. Holm, M. Chagnon, L. Pérusse, K. Lindell, B. Carlsson, C. Bouchard, and P. Björntorp Hypertension in Obesity and the Leptin Receptor Gene Locus J. Clin. Endocrinol. Metab., September 1, 2000; 85(9): 3126 - 3131. [Abstract] [Full Text]
|
|
|
|
|
|
Y. C. Chagnon, J. H. Wilmore, I. B. Borecki, J. Gagnon, L. Pérusse, M. Chagnon, G. R. Collier, A. S. Leon, J. S. Skinner, D. C. Rao, et al. Associations between the Leptin Receptor Gene and Adiposity in Middle-Aged Caucasian Males from the HERITAGE Family Study J. Clin. Endocrinol. Metab., January 1, 2000; 85(1): 29 - 34. [Abstract] [Full Text]
|
|
|
|
 |
|
 D. Chen and A. Garg Monogenic disorders of obesity and body fat distribution J. Lipid Res., October 1, 1999; 40(10): 1735 - 1746. [Abstract] [Full Text]
|
|
|
|
|
|
E. M. Gabriel, E. R. Bergert, C. S. Grant, J. A. van Heerden, G. B. Thompson, and J. C. Morris Germline Polymorphism of Codon 727 of Human Thyroid-Stimulating Hormone Receptor Is Associated with Toxic Multinodular Goiter J. Clin. Endocrinol. Metab., September 1, 1999; 84(9): 3328 - 3335. [Abstract] [Full Text]
|
|
|
|
 |
|
 W. K. Chung, K. Belfi, M. Chua, J. Wiley, R. Mackintosh, M. Nicolson, C. N. Boozer, and R. L. Leibel Heterozygosity for Lepob or Leprdb affects body composition and leptin homeostasis in adult mice Am J Physiol Regulatory Integrative Comp Physiol, April 1, 1998; 274(4): R985 - R990. [Abstract] [Full Text] [PDF]
|
|