Lower Metabolic Rate in Individuals Heterozygous for Either a Frameshift or a Functional Missense MC4R Variant

摘要: OBJECTIVE— Humans with functional variants in the melanocortin 4 receptor (MC4R) are obese, hyperphagic, and hyperinsulinemic but have been reported to no difference energy expenditure. RESEARCH DESIGN AND METHODS— We investigated association of two MC4R variants, Arg165Gln (R165Q) A insertion at nucleotide 100 (NT100), adiposity 3,074 full-heritage Pima Indians, a subset whom had metabolic measures including 24-h expenditure ( n = 252) resting rate (RMR) 364). RESULTS— Among subjects, 43 were heterozygous for R165Q 14 NT100 (frequency 0.007 0.002). Mean (± SD) BMI was higher among subjects (39.3 ± 8.6 kg/m 2 ) or (41.2 7.8) than without either variant (37.1 8.4) P 0.04 0.02, adjusted age, sex, birth year accounting family membership). The (four NT100; three R165Q) RMR (six lower only met statistical significance when combined compared variant: least-squares means, 2,163 kcal/24 h (95% CI 2,035–2,291) vs. 2,307 (2,285–2,328), 0.03 expenditure, 1,617 (1,499–1,734) 1,754 (1,736–1,772), 0.02 RMR; fat-free mass, fat mass). For RMR, this persisted, even after membership. CONCLUSIONS— Indians BMIs (by ∼140 kcal/day), indicating that component increased adiposity.