Short Communication

International Journal of Obesity (2008) 32, 1730–1735; doi:10.1038/ijo.2008.168; published online 16 September 2008

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

J A Jacobsson1, J Klovins1,2, I Kapa1,2, P Danielsson3, V Svensson3, M Ridderstråle4, U Gyllensten5, C Marcus3,6, R Fredriksson1,6 and H B Schiöth1,6

  1. 1Department of Neuroscience, Functional Pharmacology, Uppsala University, Uppsala, Sweden
  2. 2Biomedical Research and Study Centre, University of Latvia, Riga, Latvia
  3. 3Department for Clinical Science, Intervention and Technology, Karolinska Institute, Division of Pediatrics, National Childhood Obesity Centre, Stockholm, Sweden
  4. 4Department of Clinical Sciences, Lund University, Malmö, Sweden
  5. 5Department of Genetics and Pathology, University of Uppsala, Uppsala, Sweden

Correspondence: Professor H Schioth, Department of Neuroscience, Functional Pharmacology, Uppsala University, Uppsala 75124, Sweden. E-mail: helgi.schioth@neuro.uu.se

6These three authors contributed equally to this work.

Received 9 May 2008; Revised 13 August 2008; Accepted 26 August 2008; Published online 16 September 2008.

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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.

Keywords:

FTO, polymorphism, metabolic phenotypes, children, adolescents

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