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

Reinehr T, Hinney A, Nguyen TT, Hebebrand J

Vestische Hospital for Children and Adolescents, University of Witten/Herdecke, Dr. F. Steiner Str. 5, 45711 Datteln, Germany. t.reinehr@kinderklinik-datteln.de

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.

Published 28 February 2008 in Diabetes, 57(3): 623-6.
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