Sporadic mutations in melanocortin receptor 3 in morbid obese individuals.
Eur J Hum Genet
; 16(5): 581-6, 2008 May.
Article
en En
| MEDLINE
| ID: mdl-18231126
ABSTRACT
Several mutations in the melanocortin receptor 4 gene have been identified in humans and account for 3-6% of morbid obesity. In contrast, strong evidence of a causative role for melanocortin receptor 3 (MC3R) mutations are still lacking. In MC3R knockout mice, high feed efficiency rather than hyperphagia seems to contribute to increased fat mass. On the basis of this evidence, the objective of the present study was to investigate the presence of MC3R mutations in a group of 290 obese subjects (mean BMI 44.2+/-5.9 kg/m2). As a control, a group of 215 normal-weight subjects (mean BMI 22.4+/-2.7 kg/m2) was also screened. Three novel mutations in the MC3R gene (A293T, I335S and X361S) were identified among the obese patients. The mutations segregated with obesity in the members of the families studied. In vitro expression studies of each mutation demonstrated a loss of function of the I335S-mutated receptor. These findings suggest that, in humans, MC3R mutations may be a cause of a dominantly inherited form of obesity. However, this association as well as the specific phenotypic characteristics resulting from these mutations need to be further evaluated in larger series of obese subjects.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Obesidad Mórbida
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Receptor de Melanocortina Tipo 3
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Mutación
Tipo de estudio:
Observational_studies
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Prognostic_studies
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Risk_factors_studies
Límite:
Adult
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Aged
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Animals
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Eur J Hum Genet
Asunto de la revista:
GENETICA MEDICA
Año:
2008
Tipo del documento:
Article
País de afiliación:
Italia