Effect of the melanocortin-3 receptor C17A and G241A variants on weight loss in childhood obesity.
BACKGROUND
The central melanocortin system is critical for the long-term regulation of energy homeostasis. Melanocortin-3 receptor (MC3R) knock-out mice, despite being hypophagic, have increased fat mass and higher feed efficiency than do their wild-type littermates.


OBJECTIVE
The aim was to evaluate whether, in childhood obesity, MC3R variants are associated with changes in fatness reduction as a consequence of a weight-reduction program.


METHODS
Molecular screening of the MC3R coding region in 184 obese children, 77 girls and 107 boys [x (+/-SEM) body mass index (BMI; in kg/m(2)) z score: 3.3 +/- 2.3; age 9.2 +/- 2 y], was performed. BMI was evaluated at baseline and after 6 and 12 mo of the weight loss program.


RESULTS
No new mutations were found. Two previously described polymorphisms, C17A (Thr6Lys) and G241A (Val81Ile), were observed in 20 patients in almost complete linkage disequilibrium. No significant differences in BMI z scores were observed at baseline of the weight-loss program between the genotypes; however, at follow-up, heterozygotes showed a significantly higher BMI z score (P = 0.03). When the patients were divided according to the amount of weight lost, a higher prevalence of heterozygotes was observed among subjects who lowered their BMI z score <1.5 (P = 0.03).


CONCLUSIONS
These results suggest a gene-diet interaction between the MC3R C17A and G241A variants and a weight loss program for the ability to lose weight in childhood obesity.
Santoro
Nicola
N
Department of Pediatrics "F Fede," Seconda Università degli Studi di Napoli, Napoli, Italy.
Perrone
Laura
L
Cirillo
Grazia
G
Raimondo
Paolo
P
Amato
Alessandra
A
Brienza
Carmine
C
Del Giudice
Emanuele Miraglia
EM
D000273:Adipose Tissue / Q000378:metabolism; D001823:Body Composition / Q000235:genetics* / Q000502:physiology; D002648:Child; D004038:Diet, Reducing; D005260:Female; D005820:Genetic Testing; D014644:Genetic Variation; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D009765:Obesity / Q000235:genetics* / Q000378:metabolism; D011110:Polymorphism, Genetic; D044104:Receptor, Melanocortin, Type 3 / Q000235:genetics*; D015431:Weight Loss / Q000235:genetics / Q000502:physiology
D044104:Receptor, Melanocortin, Type 3