Affiliation:
1. Centre National de la Recherche Scientifique EP 10, Institut Pasteur de Lille et CHU Lille
2. Department de Nutrition Hotel-Dieu
3. Sequana Therapeutics La Jolla, California
4. Institute National de la Sante et de la Recherche Medicale U358 Paris, France
Abstract
Obesity is one of the most significant risk factors for hypertension, coronary heart disease, and NIDDM (Frayn KN, Coppack SW: Insulin resistance, adipose tissue and coronary heart disease. Clin Sci 82:1–8, 1992; Kaplan NM: The deadly quartet: upper-body obesity, glucose intolerance, 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 component (Stunkard AJ, Harris JR, Pedersen NL, McClearn GE: The body-mass index of twins who have been reared apart. N Engl J Med 322:1483–1487, 1990; Bouchard C, Despres J-P, Mauriege P: Genetic and nongenetic determinants of regional fat distribution. Endocr Rev 14:72–93, 1993), the genes and predisposing mutations remain poorly understood. This is in contrast to several well-defined genetic models for obesity in rodents, particularly the mouse obese (ob) gene, in which loss-of-function mutations cause severe obesity. Recent studies have demonstrated a substantial reduction in body fat when recombinant ob protein (leptin) is administered to mice. To test the relevance of these observations to human obesity, the location of the human homologue (OB) was established by radiation hybrid mapping and eight microsatellite markers spanning the OB gene region (7q3l.3) were genotyped in 101 obese French families. Affected–sib-pair analyses for extreme obesity, defined by BMI >35 kg/m2, revealed suggestive evidence for linkage to three markers located within 2 cM of the OB gene (D7S514, D7S680, and D7S530). The OB gene is therefore a candidate for genetic predisposition to extreme obesity in a subset of these families.
Publisher
American Diabetes Association
Subject
Endocrinology, Diabetes and Metabolism,Internal Medicine
Cited by
91 articles.
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