INDICATION FOR LINKAGE OF THE HUMAN OB GENE REGION WITH EXTREME OBESITY

Citation
K. Clement et al., INDICATION FOR LINKAGE OF THE HUMAN OB GENE REGION WITH EXTREME OBESITY, Diabetes, 45(5), 1996, pp. 687-690
Citations number
29
Categorie Soggetti
Endocrynology & Metabolism","Medicine, General & Internal
Journal title
ISSN journal
00121797
Volume
45
Issue
5
Year of publication
1996
Pages
687 - 690
Database
ISI
SICI code
0012-1797(1996)45:5<687:IFLOTH>2.0.ZU;2-Y
Abstract
Obesity is one of the most significant risk factors for hypertension, coronary heart disease, and NIDDM (Frayn RN, Coppack SW: Insulin resis tance, adipose tissue and coronary heart disease. Clin Sci 82:1-8, 199 2; Kaplan NM: The deadly quartet: upper-body obesity, glucose intolera nce, hypertriglyceridemia, and hypertension. Arch Intern Med 149:1514- 1520, 1989). While family segregation, adoption, and twin studies have indicated that degree of adiposity has a significant genetic componen t (Stunkard AJ, Harris JR, Pedersen NL, McClearn GE: The body-mass ind ex of twins who have been reared apart. N Engl J Med 322:1483-1487, 19 90; Bouchard C, Despres J-P, Mauriege P: Genetic and nongenetic determ inants of regional fat distribution. Endocr Rev 14:72-93, 1993), the g enes and predisposing mutations remain poorly understood. This is in c ontrast to several well-defined genetic models for obesity in rodents, particularly the mouse obese Cab) gene, in which loss-of-function mut ations cause severe obesity. Recent studies have demonstrated a substa ntial reduction in body fat when recombinant ob protein (leptin) is ad ministered to mice. To test the relevance of these observations to hum an obesity, the location of the human homologue (OB) was established b y radiation hybrid mapping and eight microsatellite markers spanning t he OB gene region (7q31.3) were genotyped in 101 obese French families . Affected-sib-pair analyses for extreme obesity, defined by BMI >35 k g/m(2), revealed suggestive evidence for linkage to three markers loca ted within 2 cM of the OB gene (D7S514, D7S680, and D7S530). The OB ge ne is therefore a candidate for genetic predisposition to extreme obes ity in a subset of these families.