NOVEL POLYMORPHISM OF THE HUMAN OB GENE PROMOTER IN LEAN AND MORBIDLYOBESE SUBJECTS

OBJECTIVE: Leptin, the circulating product of the human ob gene, may p lay role in control of appetite and metabolic rate. We screened the pr oximal promoter area of the ob gene for mutations and common polymorph isms in order to find out whether genetic variation in the regulatory area of this gene plays a role in human obesity. DESIGN: The technique of single-strand-conformation polymorphism (SSCP) was applied to scre en for the promoter area of the ob gene for genetic alterations in mor bidly obese patients. SUBJECTS: A total of 249 morbidity obese (presen t or past body mass index [BMI] greater than or equal to 40 kg/m(2)) a nd 141 lean (BMI less than or equal to 25 kg/m(2)) subjects. MEASUREME NTS: DNA analysis was carried out using a single-strand conformation p olymorphism (SSCP) technique and PCR followed by digestion with the re striction enzyme BssHII. Leptin was determined by radioimmunoassay in obese subjects. Serum lipids. glucose and insulin concentrations in th e obese subjects were also determined. RESULTS: A new polymorphism C(- 188)A was identified in the promoter region of the ob gene. This polym orphism was detected with allelic frequencies of 0.06 in morbidly obes e subjects and 0.09 in lean controls (P=0.28). Initial studies failed to show an association of this polymorphism with serum leptin, respons e to treatment far obesity. history and extent of weight gain, or seru m insulin, glucose of lipid concentrations. CONCLUSIONS: We have ident ified a common polymorphism in the promoter area of the human ob gene which appears to be very useful for genetic association and linkage st udies. Further studies are needed to elucidate its potential role in t he regulation of the human ob gene and in human metabolic disorders.