Endocrine Abstracts (2002) 3 P107

Single nucleotide polymorphisms in the ghrelin gene in tall obese children

M Gueorguiev1, E O'Grady2, AB Grossman1, P Froguel2 & M Korbonits1

1Department of Endocrinology, St Bartholomew's Hospital, London, UK; 2The London Genome Centre, Queen Mary and Westfield College, London, UK.

In addition to its original growth hormone-releasing function,

ghrelin has been shown to exert a variety of effects on metabolism,

specifically in terms of the regulation of body habitus and fat. It

increase food intake and body weight, and regulates energy

homeostasis: it also increases glucose levels, reduces insulin

secretion and regulates downstream insulin signalling. In a recent

study (1), three polymorphisms in the preproghrelin gene were

identified among 96 unrelated female subjects: most importantly,

an Arg51Gln 'mutation' (translated in the mature ghrelin peptide)

was identified, potentially causing a defective or inactive ghrelin

peptide, and was associated with late-onset obesity with a

prevalence of 6.3%. We therefore searched for single nucleotide

polymorphisms in ghrelin gene among 69 tall obese children

(above the third standard deviation for height and weight). These

children were selected from among a French Caucasian population

including 272 families with at least one child (proband) with body

mass index above the 97th percentile. WAVE Nucleic Acid

Fragment Analysis and direct sequencing identified 17 patients

with single nucleotide polymorphisms (SNP) from 69 subjects

studied (24.6 %; all heterozygotes): 16 (23.2%) presented the

same nucleotide change in the gene sequence at position C247A

(corresponding to codon Leu72Met of the preproghrelin gene; this

polymorphism has also been reported in non-obese subjects). One

of these patients had one additional base change at position

G185A (codon Arg51Gln of the preproghrelin gene, the last

amino-acid of the mature ghrelin protein). One (1.4%) other patient

presented with a novel nucleotide change at position C144G in the

intronic region adjacent to the exon/intron junction of exon 2. The

first two SNPs have already been reported, while the third one is

novel. These results suggest a that ghrelin may have a role as role

a candidate/ susceptibility gene for obesity.

1. Ukkola O et al. J Clin Endocrinol Metab 2001; 86: 3996-9.

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