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American Journal of Epidemiology Advance Access originally published online on June 22, 2005
American Journal of Epidemiology 2005 162(2):101-114; doi:10.1093/aje/kwi174
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American Journal of Epidemiology Copyright © 2005 by the Johns Hopkins Bloomberg School of Public Health All rights reserved

HUMAN GENOME EPIDEMIOLOGY (HuGE) REVIEW

Genetics of Leptin and Obesity: A HuGE Review

Valentina Paracchini, Paola Pedotti and Emanuela Taioli

From the Unit of Molecular and Genetic Epidemiology, Fondazione Policlinico IRCCS, Milano, Italy

Correspondence to Dr. Emanuela Taioli, Fondazione Policlinico IRCCS, Unit of Molecular and Genetic Epidemiology, Via Pace 9, Milano 20122, Italy (e-mail: taioli{at}policlinico.mi.it).

Leptin is an important regulator of the mass of adipose tissue and of body weight; it operates by inhibiting food intake and stimulating energy expenditure. Some polymorphic genes involved in the regulation of leptin—the leptin gene (LEP A19G), the leptin receptor gene (LEPR Q223R, K109R, and K656N), and the peroxisome proliferator-activated receptor-gamma gene (PPARG P12A and C161T)—have been investigated as possible factors associated with obesity. Allelic frequencies of these polymorphisms show ethnic variation. The authors performed a meta-analysis of the available data on the association between these polymorphisms and obesity based on case-control studies. Odds ratios and 95% confidence intervals for obesity associated with leptin polymorphisms were calculated by using both fixed- and random-effects models. Results suggest no evidence of association between the genes under study and obesity. The lack of association could be due to the complex pathogenesis of obesity, which involves a number of genetic and environmental factors. Large studies including testing of multiple genes in both obese and lean subjects, with epidemiologic data on dietary habits in different ethnic groups, are necessary to better understand the role of leptin in regulating weight in human populations.

epidemiology; genetics; LEP; LEPR; leptin; meta-analysis; obesity; PPARG

Abbreviations: BMI, body mass index; CI, confidence interval; LEP, leptin gene; LEPR, leptin receptor gene; PPARG, peroxisome proliferator-activated receptor-gamma gene

Editor's note: This paper is also available on the website of the Human Genome Epidemiology Network (http://www.cdc.gov/genomics/hugenet/).


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