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.

  • Original Article
  • Published:

Preproghrelin Leu72Met variant contributes to overweight in middle-aged men of a Japanese large cohort

International Journal of Obesity volume 30, pages 1609–1614 (2006)Cite this article

Abstract

Objective:

To investigate whether Leu72Met polymorphism of the preproghrelin gene is associated with overweight/obesity in middle-aged and older Japanese.

Design:

Cross-sectional analysis.

Subjects:

A total of 2238 community-dwelling middle-aged and older Japanese people (age: 40–79 years) who participated in the first wave of examinations in the National Institute for Longevity Sciences – Longitudinal Study of Aging from April 1998 to March 2000.

Measurements:

The Leu72Met polymorphism of prepoghrelin gene, anthropometric variables including body weight, body mass index (BMI), waist circumference, waist-to-hip ratio and whole-fat mass and biochemical variables including serum lipid levels, fasting plasma glucose, insulin and homeostasis model assessment for insulin resistance.

Results:

The frequencies of the Leu72Leu, Leu72Met and Met72Met alleles were 63.4, 32.7 and 4.0%, respectively. No differences in the genotype distributions of the Leu72Met polymorphism were found between genders or age groups, and no significant associations were observed between polymorphism and anthropometric variables in women and older men. However, middle-aged men who were 72Met allele carriers showed a higher body weight change from body weight at 18 years of age, as well as a higher waist circumference and a tendency to a higher waist-hip-ratio than noncarriers. Although there were no significant differences in the genotype distribution according to BMI in women and older men, a significantly higher frequency of the 72Met allele was found in the higher BMI group (BMI⩾25 kg/m2) of middle-aged men than in the normal-weight group. No significant associations were observed between polymorphism and serum lipid, glucose or insulin levels.

Conclusions:

These results suggest that the 72Met allele of the preproghrelin gene is a contributing factor for midlife weight change in men.

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

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

    Article  CAS  Google Scholar 

  3. Wren AM, Seal LJ, Cohen MA, Brynes AE, Frost GS, Murphy KG et al. Ghrelin enhances appetite and increases food intake in humans. J Clin Endocrinol Metab 2001; 86: 5992–5995.

    Article  CAS  Google Scholar 

  4. Inui A, Asakawa A, Bowers CY, Mantovani G, Laviano A, Meguid MM et al. Ghrelin, appetite, and gastric motility: the emerging role of the stomach as an endocrine organ. FASEB J 2004; 18: 439–456.

    Article  CAS  Google Scholar 

  5. Pöykkö SM, Kellokoski E, Hörkkö S, Kauma H, Kesäniemi YA, Ukkola O . Low plasma ghrelin is associated with insulin resistance, hypertension, and the prevalence of type 2 diabetes. Diabetes 2003; 52: 2546–2553.

    Article  Google Scholar 

  6. Purnell JQ, Weigle DS, Breen P, Cummings DE . Ghrelin levels correlate with insulin levels, insulin resistance, and high-density lipoprotein cholesterol, but not with gender, menopausal status, or cortisol levels in humans. J Clin Endocrinol Metab 2003; 88: 5747–5752.

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  8. Miraglia del Giudice E, Santoro N, Cirillo G, Raimondo P, Grandone A, D’Aniello A 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 Relat Metab Disord 2004; 28: 447–450.

    Article  CAS  Google Scholar 

  9. Korbonits M, Gueorguiev M, O’Grady E, Lecoeur C, Swan DC, Mein CA et al. 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 

  10. Ukkola O, Ravussin E, Jacobson P, Perusse L, Rankinen T, Tschop M et al. Role of ghrelin polymorphisms in obesity based on three different studies. Obes Res 2002; 10: 782–791.

    Article  CAS  Google Scholar 

  11. Shimokata H, Ando F, Niino N . A new comprehensive study on aging – the National Institute for Longevity Sciences, Longitudinal Study of Aging (NILS-LSA). J Epidemiol 2000; 10 (1 Suppl): S1–S9.

    Article  CAS  Google Scholar 

  12. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC . Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985; 28: 412–419.

    Article  CAS  Google Scholar 

  13. Yamada Y, Ando F, Niino N, Shimokata H . Association of polymorphisms of the osteoprotegerin gene with bone mineral density in Japanese women but not men. Mol Genet Metab 2003; 80: 344–349.

    Article  CAS  Google Scholar 

  14. Hinney A, Hoch A, Geller F, Schafer H, Siegfried W, Goldschmidt H et al. 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 

  15. Troy LM, Hunter DJ, Manson JE, Colditz GA, Stampfer MJ, Willett WC . The validity of recalled weight among younger women. Int J Obes Relat Metab Disord 1995; 19: 570–572.

    CAS  Google Scholar 

  16. Must A, Willett WC, Dietz WH . Remote recall of childhood height, weight, and body build by elderly subjects. Am J Epidemiol 1993; 138: 56–64.

    Article  CAS  Google Scholar 

  17. Ukkola O, Kesäniemi YA . Preproghrelin Leu72Met polymorphism in patients with type 2 diabetes mellitus. J Intern Med 2003; 254: 391–394.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by Research Grants for Longevity Sciences (H15-Shi-02) from the Ministry of Health, Labor, and Welfare of Japan.

Author information

Authors and Affiliations

  1. Department of Geriatrics, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya, Japan

    M Kuzuya & A Iguchi

  2. Department of Epidemiology, National Institute for Longevity Sciences, Obu, Aichi, Japan

    F Ando & H Shimokata

Authors
  1. M Kuzuya
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. F Ando
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. A Iguchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. H Shimokata
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to M Kuzuya.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kuzuya, M., Ando, F., Iguchi, A. et al. Preproghrelin Leu72Met variant contributes to overweight in middle-aged men of a Japanese large cohort. Int J Obes 30, 1609–1614 (2006). https://doi.org/10.1038/sj.ijo.0803296

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.ijo.0803296

Keywords

This article is cited by

Search

Advanced search

Quick links