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Rigshospitalet - a part of Copenhagen University Hospital
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Obesity treatment effect in Danish children and adolescents carrying Melanocortin-4 Receptor mutations

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  • Cæcilie Trier
  • Mette Hollensted
  • Theresia M Schnurr
  • Morten Asp Vonsild Lund
  • Tenna Ruest Haarmark Nielsen
  • Gao Rui
  • Ehm Astrid Andersson
  • Mathilde Svendstrup
  • Dorthe Sadowa Bille
  • Anette P Gjesing
  • Cilius Esmann Fonvig
  • Christine Frithioff-Bøjsøe
  • Marie Balslev-Harder
  • Shi Quan
  • Michael Gamborg
  • Oluf Pedersen
  • Lars Ängquist
  • Jens-Christian Holm
  • Torben Hansen
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OBJECTIVES: To determine the prevalence of Melanocortin-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, an MC4R mutation 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 unresolved MC4R mutations. 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 unresolved MC4R mutations. In contrast to noncarriers, carriers of damaging or unresolved MC4R mutations failed to reduce their BMI SDS during obesity treatment, indicating a need for personalized treatment based on the MC4R genotype.

Original languageEnglish
JournalInternational journal of obesity (2005)
Volume45
Issue number1
Pages (from-to)66-76
Number of pages11
ISSN0307-0565
DOIs
Publication statusPublished - Jan 2021

ID: 61714133