Introduction: Prader Willi Syndrome (PWS) is a genetic syndrome characterized by hyperphagia, morbid obesity, and many other endocrine alterations. PWS subjects present higher ghrelin levels. The cause of this increase as well as the modulation of ghrelin secretion at fasting and feeding in relation to other metabolic parameters in PWS is largely unknown. It has also been demonstrated that many ghrelin gene (GHRL) polymorphisms are associated with obesity, type 2 diabetes, and hypertension. Despite these data, the physiologic role of regulation of GHRL expression in normal condition as well as in PWS has not been fully clarified so far.
Subjects and methods: To this aim, mutational analysis of the total GHRL in unrelated 90 normal-weighted (CCNW), 81 obese (OB) healthy young subjects, and 34 children or adult PWS were performed. We also evaluated lipid metabolism, fasting glucose in children and glucose tolerance in adult PWS. Results. The pre-pro GHRL variants and a SNP of the promoter region (rs26802) showed similar allele frequency in CCNW, OB, and PWS. All PWS were carriers for a second common polymorphism of SNP in the promoter region (rs27647) (P<0.002 and P<0.003 in comparison to CCNP +OB, and CCNP or OB, respectively). No significant differences in rs27647 were recorded between CCNP and OB. Moreover, the rs26802 genotype (A>C) distribution was different between euglycemic and diabetic adult PWS (P<0.02). No other associations were found between the other polymorphisms and the metabolic parameters in PWS. Conclusions. These data report for the first time that polymorphisms in the 5′ flanking region of GHRL seem differently distributed in PWS compared to normal population and that they may be associated to the development of a diabetic phenotype in adult PWS.
03 - 07 May 2008
European Society of Endocrinology