title: Greater impact of melanocortin-4 receptor deficiency on rates of growth and risk of type 2 diabetes during childhood compared with adulthood in Pima Indians.
abstract: Features of melanocortin-4 receptor (MC4R) deficiency have been observed to be more pronounced in childhood. Longitudinal data from a population-based study were used to separate the phenotypic effects of MC4R deficiency during childhood and adulthood. The MC4R exon was sequenced in 6,760 individuals of predominantly Pima Indian heritage, and discovered mutations were functionally assessed in vitro. Effects on BMI, height, and slope of BMI change were assessed during childhood (ages 5-20 years) and adulthood (ages 20-45 years). Six mutations affecting MC4R function, including three that may be private to Pima Indians, were found in 159 individuals (2.4%). The slope of BMI increase was greater in individuals carrying an MC4R mutation compared with noncarriers during childhood but not during adulthood. The final adult height obtained was higher in individuals with MC4R deficiency. There was an increased risk for developing type 2 diabetes in individuals with a defective MC4R during childhood and adulthood, but this was only independent of BMI in childhood. The greater rates of body mass accumulation and risk of type 2 diabetes before the age of 20 years in individuals with MC4R deficiency indicate that the effects of these mutations are more apparent during the active growth of childhood.
authors: Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, Arizona, USA. thearlem@mail.nih.gov
authors: Marie S
authors: MS
authors: Thearle
authors: Yunhua L
authors: YL
authors: Muller
authors: Robert L
authors: RL
authors: Hanson
authors: Meghan
authors: M
authors: Mullins
authors: Maryam
authors: M
authors: Abdussamad
authors: John
authors: J
authors: Tran
authors: William C
authors: WC
authors: Knowler
authors: Clifton
authors: C
authors: Bogardus
authors: Jonathan
authors: J
authors: Krakoff
authors: Leslie J
authors: LJ
authors: Baier
mesh_terms: D000293:Adolescent; D000328:Adult; D015992:Body Mass Index; D002648:Child; D002657:Child Development; D002675:Child, Preschool; D003924:Diabetes Mellitus, Type 2 / Q000208:ethnology / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D048788:Growth and Development / Q000235:genetics*; D006801:Humans; D007198:Indians, North American / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D044105:Receptor, Melanocortin, Type 4 / Q000172:deficiency / Q000235:genetics* / Q000502:physiology; D012307:Risk Factors; D055815:Young Adult
chemical_list: C470072:MC4R protein, human; D044105:Receptor, Melanocortin, Type 4