Obesity treatment effect in Danish children and adolescents carrying Melanocortin-4 Receptor mutations

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

Objectives To determine the prevalence ofMelanocortin-4 Receptor(MC4R) mutations in a cohort of children and adolescents with overweight or obesity and to determine whether treatment responses differed between carriers and noncarriers. Methods Using target region capture sequencing, anMC4Rmutation screen was performed in 1261 Danish children and adolescents enrolled at a tertiary multidisciplinary childhood obesity treatment center. Measurements of anthropometrics, blood pressure, fasting blood biochemistry including lipid and hormone levels, and dual-energy X-ray absorptiometry were performed at baseline and throughout treatment. Results Of 1209 children and adolescents that met all criteria to be included in the described analyses, 30 (2.5%) carried damaging or unresolvedMC4Rmutations. At baseline, mutation carriers exhibited higher concentrations of plasma thyroid-stimulating hormone (p = 0.003), and lower concentrations of plasma thyroxine (p = 0.010) compared to noncarriers. After a median of 1 year of treatment (range 0.5-4.0 years), body mass index (BMI) standard deviation score (SDS) was reduced in noncarriers but not in carriers, and this difference in treatment response was statistically significant (p = 0.005). Furthermore, HDL cholesterol was reduced in carriers, a response significantly different from that of noncarriers (p = 0.017). Conclusion Among Danish children and adolescents with overweight or obesity entering a tertiary lifestyle intervention, 2.5% carried damaging or unresolvedMC4Rmutations. In contrast to noncarriers, carriers of damaging or unresolvedMC4Rmutations failed to reduce their BMI SDS during obesity treatment, indicating a need for personalized treatment based on theMC4Rgenotype.

TidsskriftInternational Journal of Obesity
Sider (fra-til)66-76
Antal sider11
StatusUdgivet - 2021

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