title: A variation in the ghrelin gene increases weight and decreases insulin secretion in tall, obese children.
abstract: Ghrelin is a recently recognized gut-brain peptide originally derived from the gastric mucosa. It stimulates growth hormone release, increases appetite and facilitates fat storage, and may interact with glucose metabolism. We studied the ghrelin gene in a group of 70 tall and obese children (mean age 9.4 year, Z body mass index [BMI] and Z height >3 and/or BMI percentile >99%). We found 10 single nucleotide polymorphisms. One common polymorphism of the ghrelin gene, which corresponds to an amino acid change in the tail of the prepro-ghrelin molecule, was significantly associated with children with a higher BMI (P = 0.001), and with lower insulin secretion during the first part of an oral glucose tolerance test (P = 0.05) although no difference in glucose levels was noted. This might suggest increased insulin sensitivity, although this is not supported by the lack of difference in fasting and 2 hour insulin levels; alternatively, this may be indicative of impaired first phase insulin secretion. These data suggest that variations in the ghrelin gene contribute to obesity in children and may modulate glucose-induced insulin secretion.
authors.affiliation: Department of Endocrinology, St. Bartholomew's Hospital, London EC1A 7BE, United Kingdom. m.koronits@qmul.ac.uk
authors.forename: Márta
authors.initials: M
authors.lastname: Korbonits
authors.forename: Maria
authors.initials: M
authors.lastname: Gueorguiev
authors.forename: Eithne
authors.initials: E
authors.lastname: O'Grady
authors.forename: Cecile
authors.initials: C
authors.lastname: Lecoeur
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Swan
authors.forename: Charles A
authors.initials: CA
authors.lastname: Mein
authors.forename: Jacques
authors.initials: J
authors.lastname: Weill
authors.forename: Ashley B
authors.initials: AB
authors.lastname: Grossman
authors.forename: Philippe
authors.initials: P
authors.lastname: Froguel
mesh_terms: D001827:Body Height / Q000235:genetics; D001835:Body Weight / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D054439:Ghrelin; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D009037:Motilin / Q000235:genetics*; D009765:Obesity / Q000235:genetics*; D036361:Peptide Hormones; D010455:Peptides / Q000235:genetics*; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide
chemical_list: D054439:Ghrelin; D007328:Insulin; D036361:Peptide Hormones; D010455:Peptides; D009037:Motilin