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Novel genetic variant in FTO influences insulin levels and insulin resistance in severely obese children and adolescents

International Journal of Obesity volume 32, pages 1730–1735 (2008)Cite this article

Abstract

Background:

The global prevalence of obesity and overweight is increasing rapidly among adults as well as among children and adolescents. Recent genome-wide association studies have provided strong support for association between variants in the FTO gene and obesity. We sequenced regions of the FTO gene to identify novel variants that are associated with obesity and related metabolic traits.

Results:

We screened exons 3 and 4 including exon–intron boundaries in FTO in 48 obese children and adolescents and identified three novel single nucleotide polymorphism in the fourth intronic region, (c.896+37A>G, c.896+117C>G and c.896+223A>G). We further genotyped c.896+223A>G in 962 subjects, 450 well-characterized obese children and adolescents and 512 adolescents with normal weight. Evidence for differences in genotype frequencies were not detected for the c.896+223A>G variant between extremely obese children and adolescents and normal weight adolescents (P=0.406, OR=1.154 (0.768–1.736)). Obese subjects with the GG genotype, however, had 30% increased fasting serum insulin levels (P=0.017) and increased degree of insulin resistance (P=0.025). There were in addition no differences in body mass index (BMI) or BMI standard deviation score (SDS) levels among the obese subjects according to genotype and the associations with insulin levels and insulin resistance remained significant when adjusting for BMI SDS.

Conclusion:

These findings suggest that this novel variant in FTO is affecting metabolic phenotypes such as insulin resistance, which are not mediated through differences in BMI levels.

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Acknowledgements

We thank Inger Jonasson, Uppsala Genome Centre, for expertise on genotyping, research coordinator Märta Fredriksson and research nurse Micaela Forssén for excellent work with the collection of normal weight adolescents. The studies were supported by the Swedish Research Council (VR, medicine), AFA Insurance, the Swedish Research Council for Working Life and Social Research, Svenska Läkarsällskapet, Åhlens Foundation, The Novo Nordisk Foundation, Swedish Royal Academy of Sciences, Borgströms Stiftelse and Magnus Bergvall Foundation. RF was supported by the Swedish Brain Research Foundation.

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Author notes

  1. C Marcus, R Fredriksson and H B Schiöth: These three authors contributed equally to this work.

Authors and Affiliations

  1. Department of Neuroscience, Functional Pharmacology, Uppsala University, Uppsala, Sweden

    J A Jacobsson, J Klovins, I Kapa, R Fredriksson & H B Schiöth

  2. Biomedical Research and Study Centre, University of Latvia, Riga, Latvia

    J Klovins & I Kapa

  3. Department for Clinical Science, Division of Pediatrics, Intervention and Technology, Karolinska Institute, National Childhood Obesity Centre, Stockholm, Sweden

    P Danielsson, V Svensson & C Marcus

  4. Department of Clinical Sciences, Lund University, Malmö, Sweden

    M Ridderstråle

  5. Department of Genetics and Pathology, University of Uppsala, Uppsala, Sweden

    U Gyllensten

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  1. J A Jacobsson
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  2. J Klovins
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  3. I Kapa
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  4. P Danielsson
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  5. V Svensson
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  6. M Ridderstråle
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  7. U Gyllensten
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  8. C Marcus
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  9. R Fredriksson
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  10. H B Schiöth
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Corresponding author

Correspondence to H B Schiöth.

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Jacobsson, J., Klovins, J., Kapa, I. et al. Novel genetic variant in FTO influences insulin levels and insulin resistance in severely obese children and adolescents. Int J Obes 32, 1730–1735 (2008). https://doi.org/10.1038/ijo.2008.168

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  • DOI: https://doi.org/10.1038/ijo.2008.168

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