Aggravating effect of INSIG2 and FTO on overweight reduction in a one-year lifestyle intervention.
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/m(2)).


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.
Reinehr
T
T
Vestische Hospital for Children and Adolescents, University of Witten/Herdecke, Dr F Steiner Strasse 5, 45711 Datteln, Germany. T.Reinehr@kinderklinik-datteln.de
Hinney
A
A
Toschke
A M
AM
Hebebrand
J
J
D000293:Adolescent; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; D015992:Body Mass Index; D002648:Child; D002675:Child, Preschool; D005260:Female; D005838:Genotype; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008019:Life Style; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D009765:Obesity / Q000235:genetics / Q000503:physiopathology / Q000628:therapy; D050177:Overweight / Q000235:genetics* / Q000503:physiopathology / Q000628:therapy; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000235:genetics*; D016896:Treatment Outcome; D015431:Weight Loss / Q000235:genetics
C467727:INSIG2 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D011506:Proteins; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; C526492:FTO protein, human