Energy intake and energy expenditure among children with polymorphisms of the melanocortin-3 receptor.
BACKGROUND
Homozygosity for 2 protein-altering polymorphisms in the melanocortin-3 receptor gene (MC3R) coding sequence, C17A and G241A, has been reported to be associated with an obesity phenotype in children, yet how these polymorphisms affect energy homeostasis is unknown. Association between adult body weight and +2138InsCAGACC, another variant in the 3' untranslated region of MC3R, has also been described.


OBJECTIVE
The objective of this study was to examine associations of C17A + G241A and +2138InsCAGACC MC3R variants with children's energy balance.


METHODS
Children aged 6-19 y were genotyped for MC3R C17A, G241A, and +2138InsCAGACC. Subjects underwent studies of energy intake from a 9835-kcal food array (n = 185), resting energy expenditure (REE) by using indirect calorimetry (n = 302), or total daily energy expenditure (TEE) by using doubly labeled water (n = 120). Linear regression was used to examine the associations between MC3R polymorphisms and the measures of energy balance.


RESULTS
Body mass index and fat mass were greater in those with double homozygosity for C17A + G241A (P = 0.001). After accounting for covariates (including body composition), the number of minor C17A + G241A alleles was associated with significantly greater energy intake (beta = +0.15, P = 0.02) but not altered REE or TEE. No significant associations were observed between +2138InsCAGACC and measures of either fat mass or energy balance.


CONCLUSIONS
C17A + G241A polymorphisms may be associated with pediatric obesity because of greater energy intake rather than because of diminished energy expenditure. +2138InsCAGACC does not appear to be associated with obesity or measures of energy balance in children.
Savastano
David M
DM
Unit on Growth and Obesity, Program on Developmental Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892-1103, USA.
Tanofsky-Kraff
Marian
M
Han
Joan C
JC
Ning
Cong
C
Sorg
Rachael A
RA
Roza
Caroline A
CA
Wolkoff
Laura E
LE
Anandalingam
Kavitha
K
Jefferson-George
Kyra S
KS
Figueroa
Roberto E
RE
Sanford
Ethan L
EL
Brady
Sheila
S
Kozlosky
Merel
M
Schoeller
Dale A
DA
Yanovski
Jack A
JA
D000273:Adipose Tissue; D000293:Adolescent; D001481:Basal Metabolism; D015992:Body Mass Index; D001835:Body Weight / Q000235:genetics*; D002648:Child; D002149:Energy Intake / Q000235:genetics*; D004734:Energy Metabolism / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D005838:Genotype; D006720:Homozygote; D006801:Humans; D016014:Linear Models; D008297:Male; D020641:Polymorphism, Single Nucleotide; D044104:Receptor, Melanocortin, Type 3 / Q000235:genetics*; D055815:Young Adult
D044104:Receptor, Melanocortin, Type 3