Abstract 578 Endocrinology & Diabetes III Platform, Sunday, 5/2

Little is known about the genes that predispose individuals to become overweight during childhood. Because genes important for energy expenditure are strong candidates as regulators of body weight, we examined an uncoupling protein 2 (UCP2) 45 bp insertion/deletion in the 3' untranslated region of exon 8 in obese children and in the non-obese children of overweight parents. We related UCP2 genotype to body composition, both by anthropometric measurements and dual energy xray absorptiometry (DXA), and to resting energy expenditure, in 81 Asian, African American and Caucasian children aged 6-10 y. There were 47 children with homozygous 45 bp deletion alleles in the 3′-untranslated region of exon 8 of UCP2 (del/del), 29 children heterozygous for the insertion allele (del/ins), and 5 children with homozygous insertions (ins/ins). Body mass index (BMI) was 24.6 ± 8.0 for ins/ins, and was significantly greater for del/ins (24.1 ± 5.9 kg/m2) than for del/del subjects (20.4 ± 4.8, p<0.005). This effect was confirmed when BMI was expressed either as standard deviation score for age, gender and race or as percentage overweight, and was independent of race and gender (ANOVA, p< 0.05). Body composition was also different according to UCP2 genotype. All body circumferences and skin fold thicknesses examined were significantly greater in del/ins than in del/del (e.g. waist circumference 72.2 ± 12.0 vs. 65.1 ± 10.7, p<0.005; suprailiac skin fold thickness 21.3 ± 10.4 vs. 15.5 ± 10.0, p<0.05). By DXA, both body fat mass (p<0.005) and percentage of total body mass that was fat (p<0.005) were significantly greater in del/ins than in del/del. Results for ins/ins were similar to del/ins. Neither resting energy expenditure, corrected for lean body mass and body fat mass, nor respiratory quotient were different according to UCP genotype.

In conclusion, we have identified a genetic variant of UCP2 that appears to be associated with childhood-onset obesity. These findings suggest that the UCP2 genetic locus is involved in determining childhood body weight.