The melanocortin 3 receptor C17A + G241A haplotype is associated with lower serum triglycerides and reduced lean mass in obese African American adults

Authors

• N Dedhia
• A Davis
• A Demidowich
• D Koutzoumis
• R Roberson
• O Galescu
• JY Jun
• D Taylor-Douglas
• S Armaiz
• S Brady
• JA Yanovski

Abstract

Background: The melanocortin 3 receptor (MC3R) likely influences energy intake, energy expenditure and nutrient partitioning to alter body composition. In vitro, the C17A(Thr6Lys)+G241A(Val81Ile) human MC3R haplotype, which has high prevalence among African Americans (AAs), impairs MC3R function. In children and recent knock-in mouse studies performed by our lab, homozygosity for this haplotype is associated with obesity and reduced lean body mass percentage. This has never been investigated in a large cohort of AA adults. Objective: We investigated whether the MC3R C17A+G241A haplotype is associated with metabolic or phenotypic consequences in overweight AA adults. Methods: A convenience sample of obese, otherwise healthy AAs was examined at the NIH Clinical Center. Genotype analyses for the MC3R allelic variant C17A+G241A were performed using Taqman assays. Body composition was assessed by dual-energy X-ray absorptiometry (DXA). Results: We studied 82 obese AAs (age 35.9±11.0y; BMI 38.6±7.1; 82% female), of whom 30.5% (n=25) were homozygous wild-type (WT), 45.1% (n=37) were heterozygous (HET) and 24.4% (n=20) were homozygous for MC3R C17A+G241A (“double mutant” or DM). DM subjects demonstrated significantly lower serum triglycerides than HET or WT subjects (65.7±7.8 vs. 93.2±5.6 vs. 81.4±6.8 mg/dL, p

Scientific Focus Area: Genetics and Genomics

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