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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

¹: Vestische Hospital for Children and Adolescents, University of Witten/Herdecke
²: Department of Child and Adolescent Psychiatry; University of Duisburg-Essen, Essen
³: Institute of Medical Biometry and Epidemiology, Philipps-University of Marburg, Marburg, Germany

Objective: Homozygotes for the C-allele of the single nucleotide polymorphism rs7566605 (SNP), which is located 10kb upstream of the insulin-induced gene 2 (INSIG2), showed a slightly increased risk to become 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.

Methods: We genotyped rs7566605 in 293 obese children (mean age 10.8y, 45% male, mean BMI 28.1 kg/m²) who presented for a one-year intervention. The reduction of SDS-BMI was compared based on an intention-to-treat analysis between the children with different genotypes. Blood pressure, triglyceride, total-, HDL- and LDL-cholesterol, insulin, and glucose concentrations 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.

Key Words: obesity • children • INSIG2 • intervention • cardiovascular risk factors

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