This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Yiannakouris, N. Articles by Mantzoros, C. S. Search for Related Content PubMed PubMed Citation Articles by Yiannakouris, N. Articles by Mantzoros, C. S.

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

Departments of Home Economics and Ecology (N.Y.) and Nutrition-Dietetics (M.Y., L.M.), Harokopio University, 17671 Athens, Greece; Division of Endocrinology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School (J.L.C., C.S.M.), Boston, Massachusetts 02215; and Department of Food Science and Human Nutrition, University of Maine (D.K.-Z.), Orono, Maine 04469

Address all correspondence and requests for reprints to: Christos S. Mantzoros, M.D., Division of Endocrinology, RN 325, Beth Israel Deaconess Medical Center, Harvard Medical School, 99 Brookline Avenue, Boston, Massachusetts 02215. E-mail: cmantzor{at}caregroup

Abstract

Genetic variation at the leptin receptor gene locus may play an important role in the pathophysiology of human obesity, a leptin-resistant state. Previous studies exploring potential associations between leptin receptor gene polymorphisms and obesity have reported conflicting results. The aim of this study was to evaluate a genetically homogeneous population for associations between body composition variables and three common leptin receptor gene polymorphisms (K109R, Q223R, and K656N) that have potential functional significance as well as to assess the contributions of these polymorphisms to the variability of obesity. One hundred and eighteen consecutively enrolled subjects (62 women: mean age, 17.5 ± 1.6 yr; body mass index range, 16.2–30.1; 56 men: mean age, 17.8 ± 1.8 yr; body mass index range, 15.4–35.9) were genotyped for the three polymorphisms, and their body mass index, sum of 4 skinfolds, fat-free mass, percent fat mass, serum leptin levels, caloric intake, fat intake, and exercise patterns were determined. Allele frequencies were estimated by the gene-counting method, and genotype distributions between 89 normal weight (body mass index, 25 kg/m²) and 29 overweight-obese (body mass index, >25 kg/m²) subjects were compared using ² test (using codominant, dominant, and recessive models). Analysis of covariance was also performed to evaluate associations between the polymorphisms and body composition variables after controlling for potential confounders. For the Q223R polymorphism, there was a higher prevalence of the R223 allele in the homozygous form among overweight-obese subjects vs. normal weight subjects (20.7% vs. 4.5%; P = 0.01). Furthermore, simple and multiple regression analyses revealed that the R223 allele in the homozygous form is a significant predictor of both body mass index (P = 0.015) and percent fat mass (P = 0.02) even after adjusting for age and gender and explains 4.5% of the variance in percent fat mass and 5% of the variance in body mass index. There was no significant difference in allele frequencies or genotype distributions for the K109R or K656N polymorphisms. These findings support the hypothesis that the Q223R polymorphism (but not the K109R or K656N polymorphism) of the leptin receptor gene is associated with obesity and predicts a small percentage of body weight and body composition variability in a genetically homogeneous population.

This article has been cited by other articles:

				M. den Hoed, M. S Westerterp-Plantenga, F. G Bouwman, E. C. Mariman, and K. R Westerterp Postprandial responses in hunger and satiety are associated with the rs9939609 single nucleotide polymorphism in FTO Am. J. Clinical Nutrition, November 1, 2009; 90(5): 1426 - 1432. [Abstract] [Full Text] [PDF]

				S. Pechlivanis, J. L. Bermejo, B. Pardini, A. Naccarati, L. Vodickova, J. Novotny, K. Hemminki, P. Vodicka, and A. Forsti Genetic variation in adipokine genes and risk of colorectal cancer Eur. J. Endocrinol., June 1, 2009; 160(6): 933 - 940. [Abstract] [Full Text] [PDF]

				L. Diller, E. J. Chow, J. G. Gurney, M. M. Hudson, N. S. Kadin-Lottick, T. I. Kawashima, W. M. Leisenring, L. R. Meacham, A. C. Mertens, D. A. Mulrooney, et al. Chronic Disease in the Childhood Cancer Survivor Study Cohort: A Review of Published Findings J. Clin. Oncol., May 10, 2009; 27(14): 2339 - 2355. [Full Text] [PDF]

				J. D. Doecke, Z. Z. Zhao, M. S. Stark, A. C. Green, N. K. Hayward, G. W. Montgomery, P. M. Webb, D. C. Whiteman, and and for the Australian Cancer Study Single Nucleotide Polymorphisms in Obesity-Related Genes and the Risk of Esophageal Cancers Cancer Epidemiol. Biomarkers Prev., April 1, 2008; 17(4): 1007 - 1012. [Abstract] [Full Text] [PDF]

				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]

				V. M. Chia, P. A. Newcomb, J. W. Lampe, E. White, M. T. Mandelson, A. McTiernan, and J. D. Potter Leptin Concentrations, Leptin Receptor Polymorphisms, and Colorectal Adenoma Risk Cancer Epidemiol. Biomarkers Prev., December 1, 2007; 16(12): 2697 - 2703. [Abstract] [Full Text] [PDF]

				S. Y. Pan, Y. Mao, A.-M. Ugnat, and and the Canadian Cancer Registries Epidemiology Re Physical Activity, Obesity, Energy Intake, and the Risk of Non-Hodgkin's Lymphoma: A Population-based Case-Control Study Am. J. Epidemiol., December 15, 2005; 162(12): 1162 - 1173. [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]

				J. D. Veldhuis, J. N. Roemmich, E. J. Richmond, A. D. Rogol, J. C. Lovejoy, M. Sheffield-Moore, N. Mauras, and C. Y. Bowers Endocrine Control of Body Composition in Infancy, Childhood, and Puberty Endocr. Rev., February 1, 2005; 26(1): 114 - 146. [Abstract] [Full Text] [PDF]

				J. A. Ross, K. C. Oeffinger, S. M. Davies, A. C. Mertens, E. K. Langer, W. R. Kiffmeyer, C. A. Sklar, M. Stovall, Y. Yasui, and L. L. Robison Genetic Variation in the Leptin Receptor Gene and Obesity in Survivors of Childhood Acute Lymphoblastic Leukemia: A Report From the Childhood Cancer Survivor Study J. Clin. Oncol., September 1, 2004; 22(17): 3558 - 3562. [Abstract] [Full Text] [PDF]

				J. Ross Looking Farther Afield Cancer Epidemiol. Biomarkers Prev., June 1, 2004; 13(6): 906 - 907. [Full Text] [PDF]

				C. F. Skibola, E. A. Holly, M. S. Forrest, A. Hubbard, P. M. Bracci, D. R. Skibola, C. Hegedus, and M. T. Smith Body Mass Index, Leptin and Leptin Receptor Polymorphisms, and Non-Hodgkin Lymphoma Cancer Epidemiol. Biomarkers Prev., May 1, 2004; 13(5): 779 - 786. [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]

				Y.-J. Liu, F.-H. Xu, H. Shen, Y.-Z. Liu, H.-Y. Deng, L.-J. Zhao, Q.-Y. Huang, V. Dvornyk, T. Conway, K. M. Davies, et al. A Follow-Up Linkage Study for Quantitative Trait Loci Contributing to Obesity-Related Phenotypes J. Clin. Endocrinol. Metab., February 1, 2004; 89(2): 875 - 882. [Abstract] [Full Text] [PDF]