Evidence of an influence of a polymorphism near the INSIG2 on weight loss during a lifestyle intervention in obese children and adolescents.

OBJECTIVE Homozygotes for the C-allele of the single nucleotide polymorphism (SNP) rs7566605, located approximately 10 kb upstream of insulin-induced gene 2 (INSIG2), showed a slightly increased risk of becoming obese. The aim of this study was to analyze whether children homozygous for the C-allele lose less weight in an intervention than children with the GG- or GC-genotype. RESEARCH DESIGN AND METHODS We genotyped rs7566605 in 293 obese children (mean age 10.8 years, 45% male, mean BMI 28.1 kg/m(2)) who presented for a 1-year intervention. The reduction of SD score (SDS) BMI was compared based on an intention-to-treat analysis between the children with different genotypes. Blood pressure, triglycerides, insulin and glucose concentrations, and total, HDL, and LDL cholesterol were measured before and after intervention. RESULTS After 1 year, obese children with the CC-genotype had reduced their SDS BMI to a lower extent than obese children with GC- or GG-genotypes (recessive model P = 0.007). There was no evidence for an association of rs7566605 with the cardiovascular risk factor profile (nominal P > 0.1). CONCLUSIONS CC-homozygotes at SNP rs7566605 in the vicinity of INSIG2 lost less weight in this lifestyle intervention. This finding further implicates this polymorphism in weight regulation.