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Trier C, Hollensted M, Schnurr TM, et al. Obesity treatment effect in Danish children and adolescents carrying Melanocortin-4 Receptor mutations. Int J Obes (Lond). 2020;45(1):66-76doi: 10.1038/s41366-020-00673-6.
Trier, C., Hollensted, M., Schnurr, T. M., Lund, M. A. V., Nielsen, T. R. H., Rui, G., Andersson, E. A., Svendstrup, M., Bille, D. S., Gjesing, A. P., Fonvig, C. E., Frithioff-Bøjsøe, C., Balslev-Harder, M., Quan, S., Gamborg, M., Pedersen, O., Ängquist, L., Holm, J. C., & Hansen, T. (2021). Obesity treatment effect in Danish children and adolescents carrying Melanocortin-4 Receptor mutations. International journal of obesity (2005), 45(1), 66-76. https://doi.org/10.1038/s41366-020-00673-6
Trier, Cæcilie, et al. "Obesity treatment effect in Danish children and adolescents carrying Melanocortin-4 Receptor mutations." International journal of obesity (2005) vol. 45,1 (2021): 66-76. doi: https://doi.org/10.1038/s41366-020-00673-6
Trier C, Hollensted M, Schnurr TM, Lund MAV, Nielsen TRH, Rui G, Andersson EA, Svendstrup M, Bille DS, Gjesing AP, Fonvig CE, Frithioff-Bøjsøe C, Balslev-Harder M, Quan S, Gamborg M, Pedersen O, Ängquist L, Holm JC, Hansen T. Obesity treatment effect in Danish children and adolescents carrying Melanocortin-4 Receptor mutations. Int J Obes (Lond). 2021 Jan;45(1):66-76. doi: 10.1038/s41366-020-00673-6. Epub 2020 Sep 13. PMID: 32921795; PMCID: PMC7752754.
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Int J Obes (Lond). 2021 Jan;45(1):66-76. doi: 10.1038/s41366-020-00673-6. Epub 2020 Sep 13.

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

International journal of obesity (2005)

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

Affiliations

  1. Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
  2. The Children's Obesity Clinic, Department of Pediatrics, Copenhagen University Hospital Holbæk, Holbæk, Denmark.
  3. Department of Pediatrics, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
  4. Danish Diabetes Academy, Odense, Denmark.
  5. Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
  6. Geneplus, Bejing Institute, Bejing, China.
  7. Department of Pediatrics, Kolding Hospital a part of Lillebælt Hospital, Kolding, Denmark.
  8. BGI-Shenzhen, Shenzhen, China.
  9. Ferring Pharmaceuticals, Copenhagen, Denmark.
  10. The Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
  11. Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. [email protected].

PMID: 32921795 PMCID: PMC7752754 DOI: 10.1038/s41366-020-00673-6

Abstract

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.

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