Obesity - is it a genetic disorder?

被引:151
作者
Loos, RJF [1 ]
Bouchard, C [1 ]
机构
[1] Pennington Biomed Res Ctr, Human Genom Lab, Baton Rouge, LA 70808 USA
关键词
candidate genes; familial risk; genetic testing; genetics; obesity; positional cloning;
D O I
10.1046/j.1365-2796.2003.01242.x
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Obesity is one of the most pressing problems in the industrialized world. Twin, adoption and family studies have shown that genetic factors play a significant role in the pathogenesis of obesity. Rare mutations in humans and model organisms have provided insights into the pathways involved in body weight regulation. Studies of candidate genes indicate that some of the genes involved in pathways regulating energy expenditure and food intake may play a role in the predisposition to obesity. Amongst these genes, sequence variations in the adrenergic receptors, uncoupling proteins, peroxisome proliferator-activated receptor, and the leptin receptor genes are of particular relevance. Results that have been replicated in at least three genome-wide scans suggest that key genes are located on chromosomes 2p, 3q, 5p, 6p, 7q, 10p, 11q, 17p and 20q. We conclude that the currently available evidence suggests four levels of genetic determination of obesity: genetic obesity, strong genetic predisposition, slight genetic predisposition, and genetically resistant. This growing body of research may help in the development of anti-obesity agents and perhaps genetic tests to predict the risk for obesity.
引用
收藏
页码:401 / 425
页数:25
相关论文
共 234 条
[61]   Metabolism - Partial leptin deficiency and human adiposity [J].
Farooqi, IS ;
Keogh, JM ;
Kamath, S ;
Jones, S ;
Gibson, WT ;
Trussell, R ;
Jebb, SA ;
Lip, GYH ;
O'Rahilly, S .
NATURE, 2001, 414 (6859) :34-35
[62]   Quantitative-trait loci influencing body-mass index reside on chromosomes 7 and 13: The National Heart, Lung, and Blood Institute Family Heart Study [J].
Feitosa, MF ;
Borecki, IB ;
Rich, SS ;
Arnett, DK ;
Sholinsky, P ;
Myers, RH ;
Leppert, M ;
Province, MA .
AMERICAN JOURNAL OF HUMAN GENETICS, 2002, 70 (01) :72-82
[63]   The TNF-alpha gene Nco I polymorphism influences the relationship among insulin resistance, percent body fat, and increased serum leptin levels [J].
FernandezReal, JM ;
Gutierrez, C ;
Ricart, W ;
Casamitjana, R ;
FernandezCastaner, M ;
Vendrell, J ;
Richart, C ;
Soler, J .
DIABETES, 1997, 46 (09) :1468-1472
[64]   Trp64Arg polymorphism of the β3-adrenergic receptor gene in pregnancy:: Association with mild gestational diabetes mellitus [J].
Festa, A ;
Krugluger, W ;
Shnawa, N ;
Hopmeier, P ;
Haffner, SM ;
Schernthaner, G .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1999, 84 (05) :1695-1699
[65]   Overweight and obesity in the United States: prevalence and trends, 1960-1994 [J].
Flegal, KM ;
Carroll, MD ;
Kuczmarski, RJ ;
Johnson, CL .
INTERNATIONAL JOURNAL OF OBESITY, 1998, 22 (01) :39-47
[66]   Obesity and the hypothalamus: Novel peptides for new pathways [J].
Flier, JS ;
Maratos-Flier, E .
CELL, 1998, 92 (04) :437-440
[67]   Glucagon-like peptide 1 promotes satiety and suppresses energy intake in humans [J].
Flint, A ;
Raben, A ;
Astrup, A ;
Holst, JJ .
JOURNAL OF CLINICAL INVESTIGATION, 1998, 101 (03) :515-520
[68]   Additive effects of the mutations in the β3-adrenergic receptor and uncoupling protein-1 genes on weight loss and weight maintenance in Finnish women [J].
Fogelholm, M ;
Valve, R ;
Kukkonen-Harjula, K ;
Nenonen, A ;
Hakkarainen, V ;
Laakso, M ;
Uusitupa, M .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1998, 83 (12) :4246-4250
[69]   Environmental influences on eating and physical activity [J].
French, SA ;
Story, M ;
Jeffery, RW .
ANNUAL REVIEW OF PUBLIC HEALTH, 2001, 22 :309-335
[70]   Proteolytic cleavage product of 30-kDa adipocyte complement-related protein increases fatty acid oxidation in muscle and causes weight loss in mice [J].
Fruebis, J ;
Tsao, TS ;
Javorschi, S ;
Ebbets-Reed, D ;
Erickson, MRS ;
Yen, FT ;
Bihain, BE ;
Lodish, HF .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (04) :2005-2010