GENETIC-STUDIES OF NEUROPEPTIDE-Y AND NEUROPEPTIDE-Y RECEPTORS Y1 ANDY5 REGIONS IN MORBID-OBESITY

Synthesis and release of neuropeptide Y (NPY) are both regulated by le ptin binding to its hypothalamic receptor mediating some of the effect s of leptin on food intake. Moreover, NPY administration is a powerful stimulant of feeding behaviour. Thus, we investigated the potential i mplication of NPY, NPY-Y1 and -Y5 subtype receptors [rNPY-Y1/-Y5] in t he development of human obesity. Two complementary genetic approaches were used: 1) linkage analyses between obesity and polymorphic markers located nearby NPY and rNPY-Y1/-Y5 genes (respectively on chromosomes 7p15.1 and 4q[31.3-32]) in 93 French Caucasian morbidly obese familie s; 2) single strand conformation polymorphism (SSCP) scanning of the c oding region of the NPY and rNPY-Y1 genes performed in 50 unrelated ob ese patients ascertained on the basis of a body mass index of 27 kg/m( 2) or more and a family history of obesity. No evidence of linkage bet ween morbid obesity or obesity-related quantitative traits and NPY and rNPY-Y1/Y5 regions was found in this population. Moreover, SSCP scann ing revealed no mutation in the coding region of NPY and rNPY-Y1 genes among obese subjects. These results suggest that NPY and NPY-Y1/Y5 re ceptors are unlikely to be implicated in the development of human morb id obesity, at least in the French Caucasian population.