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Aggravating effect of INSIG2 and FTO on overweight reduction in a one-year lifestyle intervention
  1. T Reinehr1,
  2. A Hinney2,
  3. A M Toschke3,
  4. J Hebebrand2
  1. 1
    Vestische Hospital for Children and Adolescents, University of Witten/Herdecke, Datteln, Germany
  2. 2
    Department of Child and Adolescent Psychiatry; University of Duisburg, Essen, Germany
  3. 3
    King’s College London, Division of Health and Social Care Research, London, UK
  1. Correspondence to Dr P D T Reinehr, Vestische Hospital for Children and Adolescents, University of Witten/Herdecke, Dr F Steiner Strasse 5, 45711 Datteln, Germany; T.Reinehr{at}


Objective: Obesity is considered a polygenic and multifactorial disorder and different single nucleotide polymorphisms (SNP) are involved. Studies concerning their impact on weight loss in lifestyle intervention are scarce.

Methods: The effect of two different SNP (INSIG2: rs7566605, FTO: rs9939609) was analysed on the change of weight status in a one-year lifestyle intervention among 280 overweight children (mean age 10.8 years, mean body mass index (BMI) 28.1 kg/m2).

Results: The children reduced their mean SDS-BMI by −0.28 (95% CI −0.32 to −0.23). Modelling the impact of different genotypes and their statistical interactions on SDS-BMI change adjusting for age, gender and baseline BMI or SDS-BMI, respectively, revealed that the combination of the CC genotype in INSIG2 and the AA genotype in FTO was significantly associated with the lowest degree of overweight reduction, but even with an increase in overweight (SDS-BMI change +0.51; 95% CI 0.22 to 0.79).

Conclusions: These findings provide some evidence that the effects of different genotypes aggravate each other concerning weight change.

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  • This study is registered at (NCT00435734).

  • Funding This work was supported by grants from the German Ministry of Education and Research (Bundesministerium für Bildung und Forschung; National Genome Research Network, NGFN1, 2 and NGFNplus), the European Union (FP6 LSHMCT-2003-503041) and the Deutsche Forschungsgemeinschaft (DFG; HE 1446/4-1).

  • Competing interests None.

  • Ethics approval The local ethics committees of the Universities of Witten/Herdecke and Duisburg-Essen approved this study.

  • Patient consent Obtained.

  • Provenance and peer review Not commissioned; externally peer reviewed.