MARKERS FOR THE GENE OB AND SERUM LEPTIN LEVELS IN HUMAN MORBID-OBESITY

Leptin, the product of the ob gene, reduces body fat in genetically ob ese animals and circulates in elevated concentrations in the blood of obese patients, Polymorphic markers situated in the proximity of the h uman ob gene have recently been suggested to be linked to morbid obesi ty. We have studied the possible association between the microsatellit e markers near the ob gene and morbid obesity in 252 morbidly obese pa tients with a mean body mass index (BMI) of 43 +/- 7 kg/m(2), and 151 lean controls with a mean BMI of 22 +/- 2 kg/m(2), and searched for li nkage of these gene markers to obesity in 76 affected sib-pairs (BMI g reater than or equal to 32). No significant association was observed b etween any of the eight microsatellite markers and morbid obesity, and affected-sib-pair analysis failed to show linkage of three selected o b gene markers to obesity in the sibships. There was a strong positive correlation between serum leptin levels and BMI in mor morbidly obese patients; a carrier status for either of the two most prevalent allel es of the microsatellite marker D7S530 in the vicinity of the ob gene was associated with serum leptin levels in the obese subjects, Two of the markers (D7S2519, D7S649) showed a significant relation to the wei ght-losing response to a 16-week very-low-calorie dietary intervention . We have thus been able to confirm a tight relationship between serum leptin and body mass but have found no evidence for genetic linkage o f the ob gene markers to morbid obesity in a population considered to represent a genetic isolate and to be an ideal model for studies of co mplex disorders.