Obesity treatment effect in Danish children and adolescents carrying Melanocortin-4 Receptor mutations
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Obesity treatment effect in Danish children and adolescents carrying Melanocortin-4 Receptor mutations. / Trier, Cæcilie; Hollensted, Mette; Schnurr, Theresia M.; Lund, Morten Asp Vonsild; Nielsen, Tenna Ruest Haarmark; Rui, Gao; Andersson, Ehm Astrid; Svendstrup, Mathilde; Bille, Dorthe Sadowa; Gjesing, Anette P.; Fonvig, Cilius Esmann; Frithioff-Bojsoe, Christine; Balslev-Harder, Marie; Quan, Shi; Gamborg, Michael; Pedersen, Oluf; Ängquist, Lars; Holm, Jens-Christian; Hansen, Torben.
In: International Journal of Obesity, Vol. 45, 2021, p. 66-76.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Obesity treatment effect in Danish children and adolescents carrying Melanocortin-4 Receptor mutations
AU - Trier, Cæcilie
AU - Hollensted, Mette
AU - Schnurr, Theresia M.
AU - Lund, Morten Asp Vonsild
AU - Nielsen, Tenna Ruest Haarmark
AU - Rui, Gao
AU - Andersson, Ehm Astrid
AU - Svendstrup, Mathilde
AU - Bille, Dorthe Sadowa
AU - Gjesing, Anette P.
AU - Fonvig, Cilius Esmann
AU - Frithioff-Bojsoe, Christine
AU - Balslev-Harder, Marie
AU - Quan, Shi
AU - Gamborg, Michael
AU - Pedersen, Oluf
AU - Ängquist, Lars
AU - Holm, Jens-Christian
AU - Hansen, Torben
PY - 2021
Y1 - 2021
N2 - 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.
AB - 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.
KW - MELANOCORTIN-4 RECEPTOR MUTATIONS
KW - AGOUTI-RELATED PROTEIN
KW - PROOPIOMELANOCORTIN-DERIVED AGONISTS
KW - MELANOCYTE-STIMULATING HORMONE
KW - FUNCTIONAL-CHARACTERIZATION
KW - GENE-MUTATIONS
KW - PHARMACOLOGICAL CHARACTERIZATION
KW - INDUCED SUPPRESSION
KW - PUBERTAL CHANGES
KW - HIGH PREVALENCE
U2 - 10.1038/s41366-020-00673-6
DO - 10.1038/s41366-020-00673-6
M3 - Journal article
C2 - 32921795
VL - 45
SP - 66
EP - 76
JO - International Journal of Obesity
JF - International Journal of Obesity
SN - 0307-0565
ER -
ID: 249867201