RAPID COMMUNICATIONS: Mutations in the Preproghrelin/Ghrelin Gene Associated with Obesity in Humans

• DOI: 10.1210/jcem.86.8.7914
• Publication Date: 2014-01-08T17:07:29Z
• Authors: Olavi Ukkola; Eric Ravussin; Peter Jacobson; Eric E. Snyder; Monique Chagnon; Lars Sjöström; Claude Bouchard
• Keywords: Coding region

Ghrelin and preproghrelin sequences were determined in 96 unrelated female subjects with severe obesity (mean body mass index (BMI) 42.3 +/- 3.4 kg/m(2)) non-obese controls BMI 23.0 1.4 (kg/m2) of the Swedish Obese Subjects cohort. A mutation at amino acid position 51 (Arg51Gln) sequence that corresponds to last mature ghrelin product was identified six (all heterozygotes) obese (6.3%) but not among (p < 0.05). The self-reported weight 20, 30, 40 years age tended be 7.5, 4.7 6.4 kg lower, respectively, Gln allele carriers versus non-carriers. In addition, a codon 72 gene (Leu72Met) detected 15 (12 hetero- 3 homozygotes) 12 control subjects. This outside coding region associated lower onset (15.6 7.9 vs. 20.5 10.5 years; p = 0.09). addition these two mutations regions, G274A base change non-coding between exons one found only individuals. Arg51Gln substitution may alter cleavage site endoproteases length product. functional significance Leu72Met remains determined. conclusion, data provide evidence low frequency variation could play role etiology obesity.