Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Paper
  • Published:

Molecular screening of the ghrelin gene in Italian obese children: the Leu72Met variant is associated with an earlier onset of obesity

International Journal of Obesity volume 28, pages 447–450 (2004)Cite this article

Abstract

OBJECTIVE: To test whether ghrelin variants could play a role in modulating some aspects of the obese phenotype during childhood.

DESIGN: We screened the ghrelin gene in 300 Italian obese children and adolescents (mean age 10.5±3.2 y; range 4–19 y) and 200 controls by using the single-strand conformation polymorphism and the restriction fragment length polymoprhism analysis.

RESULTS: No mutations were detected with the exception of two previously described polymorphisms, Arg51Gln and Leu72Met. For both variations, allelic frequencies were similar between patients and controls. Interestingly, we showed that the Leu72Met polymorphism was associated with differences in the age at obesity onset. Patients with the Met72 allele became obese earlier than homozygous patients for the wild Leu72 allele. The logrank test comparing the plots of the complement of Kaplan–Meier estimates between the two groups of patients was statistically significant (P<0.0001).

CONCLUSION: It is unlikely that ghrelin variations cause the obesity due to single-gene mutations. The Leu72Met polymorphism of the ghrelin gene seems to play a role in anticipating the onset of obesity among children suggesting, therefore, that ghrelin may be involved in the pathophysiology of human adiposity.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1

Similar content being viewed by others

References

  1. Kojima M, Hosoda H, Date Y, Nakazato M, Matsuo H, Kangawa K . Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature 1999; 402: 656–660.

    Article  CAS  Google Scholar 

  2. Takaya K, Ariyasu H, Kanamoto N, Iwakura H, Yoshimoto A, Harada M, Mori K, Komatsu Y, Usui T, Shimatsu A, Ogawa Y, Hosoda K, Akamizu T, Kojima M, Kangawa K, Nakao K . strongly stimulates growth hormone (GH) release in humans. J Clin Endoctinol Metab 2000; 85: 4908–4911.

    Article  CAS  Google Scholar 

  3. Toogood AA, Thorner MO . Ghrelin, not just another growth hormone secretagogue. Clin Endocrinol 2001; 55: 589–591.

    Article  CAS  Google Scholar 

  4. Horvath TL, Diano S, Sotonyi P, Heiman M, Tschop M . Minireview: ghrelin and the regulation of energy balance—A hypothalamic perspective. Endocrinology 2001; 142: 4163–4169.

    Article  CAS  Google Scholar 

  5. Tschop M, Smiley DL, Heiman ML . Ghrelin induces adiposity in rodents. Nature 2000; 407: 908–913.

    Article  CAS  Google Scholar 

  6. Wren AM, Seal LJ, Cohen MA, Brynes AE, Frost GS, Murphy KG, Dhillo WS, Ghatei MA, Bloom SR . Ghrelin enhances appetite and increases food intake in humans. J Clin Endocrinol Metab 2001; 86: 5992–5995.

    Article  CAS  Google Scholar 

  7. Lawrence CB, Snape AC, Baudoin FMH, Luckman SM . Acute central ghrelin and GH secretagogues induce feeding and activate brain appetite centers. Endocrinology 2002; 143: 155–162.

    Article  CAS  Google Scholar 

  8. Tschop M, Weyer C, Tataranni PA, Devanarayan V, Ravussin E, Heiman ML . Circulating ghrelin levels are decreased in human obesity. Diabetes 2001; 50: 707–709.

    Article  CAS  Google Scholar 

  9. Nakazato M, Murakami N, Date Y, Kojima M, Kangawa K, Matsukura S . A role for ghrelin in the central regulation of feeding. Nature 2001; 409: 194–198.

    Article  CAS  Google Scholar 

  10. Schwartz MW, Woods SC, Porte Jr D, Seeley RJ, Baskin DG . Central nervous system control of food intake. Nature 2000; 404: 661–671.

    Article  CAS  Google Scholar 

  11. Sokol RJ . The chronic disease of childhood obesity: the sleeping giant has awakened (editorial). J Pediatr 2000; 136: 711–713.

    Article  Google Scholar 

  12. Stunkard AJ, Harris JR, Pedersen NL, McClearen GE . The body mass index of twins who have been reared apart. N Eng J Med 1990; 322: 1483–1487.

    Article  CAS  Google Scholar 

  13. Chagnon YC, Rankinen T, Snyder EE, Weisnagel SJ, Perusse L, Bouchard C . The human obesity gene map: the 2002 update. Obes Res 2003; 11: 313–367.

    Article  CAS  Google Scholar 

  14. Rolland-Cachera MF, Cole TJ, Sempé M, Tichet J, Rossignol C, Charraud A . Variation of the Wt/Hr2 index from birth to 87 years. Eur J Clin Nutr 1991; 45: 13–21.

    CAS  Google Scholar 

  15. Wajanrajch MP, Ten IS, Gertner JM, Leibel RL . Genomic organization of human ghrelin gene. J Endocr Genet 2000; 1: 231–233.

    Google Scholar 

  16. Miraglia del Giudice E, Santoro N, Cirillo G, D’Urso L, Di Toro R, Perrone L . Mutational screening of the Cart gene in obese children. Identifying a mutation (Leu34Phe) associated with reduced resting energy expenditure and cosegregating with obesity phenotype in a large family. Diabetes 2001; 50: 2157–2160.

    Article  Google Scholar 

  17. Ukkola O, Ravussin E, Jacobson P, Snyder EE, Chagnon M, Sjostrom L, Bouchard C . Mutations in the preproghrelin/ghrelin gene associated with obesity in humans. J Clin Endocrinol Metab 2001; 86: 3996–3999.

    Article  CAS  Google Scholar 

  18. Korbonits M, Gueorguiev M, O'Grady E, Lecoeur C, Swan DC, Mein CA, Weill J, Grossman AB, Froguel P . A variation in the ghrelin gene increases weight and decreases insulin secretion in tall, obese children. J Clin Endocrinol Metab 2002; 87: 4005–4008.

    Article  CAS  Google Scholar 

  19. Hinney A, Hoch A, Geller F, Schafer H, Siegfried W, Goldschmidt H, Remschmidt H, Hebebrand J . Ghrelin gene: identification of missense variants and a frameshift mutation in extremely obese children and adolescents and healthy normal weight students. J Clin Endocrinol Metab 2002; 87: 2716–2719.

    Article  CAS  Google Scholar 

  20. Kaiya H, Kojima M, Hosoda H, Koda A, Yamamoto K, Kitajima Y, Matsumoto M, Minamitake Y, Kikuyama S, Kangawa K . Bullfrog ghrelin is modified by n-octanoic acid at its third threonine residue. J Biol Chem 2001; 44: 40441–40448.

    Article  Google Scholar 

  21. Salbe AD, Weyer C, Lindsay RS, Ravussin E, Tataranni PA . Assessing risk factors for obesity between childood and adolescence: I. Birth weight, childood adiposity, parental obesity, insulin and leptin. Pediatrics 2002; 110: 299–306.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pediatrics, Second University of Napoli, Napoli, Italy

    E Miraglia del Giudice, N Santoro, G Cirillo, P Raimondo, A Grandone, A D'Aniello, M Di Nardo & L Perrone

Authors
  1. E Miraglia del Giudice
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. N Santoro
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. G Cirillo
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. P Raimondo
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. A Grandone
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. A D'Aniello
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. M Di Nardo
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. L Perrone
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to E Miraglia del Giudice.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Giudice, E., Santoro, N., Cirillo, G. et al. Molecular screening of the ghrelin gene in Italian obese children: the Leu72Met variant is associated with an earlier onset of obesity. Int J Obes 28, 447–450 (2004). https://doi.org/10.1038/sj.ijo.0802572

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.ijo.0802572

Keywords

This article is cited by

Search

Advanced search

Quick links