Ghrelin gene polymorphisms and ghrelin, insulin, IGF-I, leptin and anthropometric data in children and adolescents

Background: Previous investigations on the ghrelin gene reported three common polymorphisms (Arg51Gln, Leu72Met, and Gln90Leu), but their role in overweight and obese individuals remains to be clarified. Objective: To ascertain whether these genetic variants could influence ghrelin secretion and play a part in predisposing to earlier onset of obesity or in modulating the overweight phenotype in childhood. Design and methods: Mutational analysis of the entire ghrelin gene and total and acylated plasma determinations were performed in 81 obese or overweight children and adolescents (46 were obese and 35 overweight: Ob/Ow). We also recruited 168 normal-weight healthy controls (72 young adults and 96 children) for mutational or plasma ghrelin analysis. Results: Median total and acylated plasma ghrelin concentrations were significantly lower in Ob/Ow individuals than in controls (175 pg/ml compared with 345 pg/ml, P < 0.0001, and 95 pg/ml compared with 114 pg/ml, P < 0.0001, respectively). The ghrelin gene variants showed similar allele frequencies in the Ob/Ow individuals and in controls; in the former, they were not associated with any change in total and acylated circulating ghrelin concentrations or anthropometric data. The Leu72Met status was associated with a positive family history for obesity (75% for Leu72Met compared with 39% for Leu72Leu, P = 0.03) and with a greater percentage of newborns born 'large for gestational age' (33% for Leu72Met compared with 5% for Leu72Leu, P = 0.03), but in the control group it was related to a lower mean body mass index z-score (-0.03 for Leu72Met and -0.47 for Leu72Leu, P = 0.04). Conclusion: Our present findings do not support the hypothesis that the ghrelin gene polymorphisms have a relevant impact in the secretion of total and acylated ghrelin.