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WEDNESDAY, Nov. 30 (HealthDay News) -- The effects of melanocortin-4-receptor (MC4R) deficiency on the body mass accumulation rate are more pronounced during childhood, according to a study published online Nov. 21 in Diabetes.
Marie S. Thearle, M.D., from the National Institute of Diabetes and Digestive and Kidney Diseases in the National Institutes of Health in Phoenix, and colleagues conducted a longitudinal population-based study to evaluate the phenotypic effects of MC4R deficiency during childhood and adulthood. Direct sequencing of the MC4R exon was performed in 6,760 individuals of predominantly Pima Indian heritage. This was followed by in vitro functional assessments of discovered mutations. They evaluated the impact on body mass index (BMI), the slope of BMI change, and height during childhood (ages 5 to 20 years) and adulthood (ages 20 to 45 years).
The investigators identified 159 individuals with six mutations affecting MC4R function, of which three were likely to be exclusive to Pima Indians. Carriers of an MC4R mutation had greater increments in the slope of BMI increase than noncarriers, but this was only seen during childhood. Individuals with MC4R deficiency obtained a higher final adulthood height. The risk of developing type 2 diabetes was elevated among individuals with a defective MC4R during both childhood and adulthood, and this association was independent of childhood BMI.
"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," the authors write.
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