Loss-of-function mutations in the melanocortin 4 receptor in a UK birth cohort.
Nat Med
; 27(6): 1088-1096, 2021 06.
Article
em En
| MEDLINE
| ID: mdl-34045736
ABSTRACT
Mutations in the melanocortin 4 receptor gene (MC4R) are associated with obesity but little is known about the prevalence and impact of such mutations throughout human growth and development. We examined the MC4R coding sequence in 5,724 participants from the Avon Longitudinal Study of Parents and Children, functionally characterized all nonsynonymous MC4R variants and examined their association with anthropometric phenotypes from childhood to early adulthood. The frequency of heterozygous loss-of-function (LoF) mutations in MC4R was ~1 in 337 (0.30%), considerably higher than previous estimates. At age 18 years, mean differences in body weight, body mass index and fat mass between carriers and noncarriers of LoF mutations were 17.76 kg (95% CI 9.41, 26.10), 4.84 kg m-2 (95% CI 2.19, 7.49) and 14.78 kg (95% CI 8.56, 20.99), respectively. MC4R LoF mutations may be more common than previously reported and carriers of such variants may enter adult life with a substantial burden of excess adiposity.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Peso Corporal
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Predisposição Genética para Doença
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Receptor Tipo 4 de Melanocortina
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Obesidade
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article