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Associations between uncoupling protein 2, body composition, and resting energy expenditure in lean and obese African American, white, and Asian children^1,2,3

¹ From the Unit on Growth and Obesity, Developmental Endocrinology Branch, National Institute of Child Health and Human Development; the Division of Nutrition Research Coordination and the Nutrition Department, Warren Grant Magnuson Clinical Center, the National Institutes of Health, Bethesda, MD; and the Rowe Program in Genetics and Department of Pediatrics, University of California, Davis.

Background: Little is known about genes that affect childhood body weight.

Objective: The objective of this study was to examine the association between alleles of the mitochondrial uncoupling protein 2 (UCP2) gene and obesity because UCP2 may influence energy expenditure.

Design: We related UCP2 genotype to body composition and resting energy expenditure in 105 children aged 6–10 y. Overweight children and nonoverweight children of overweight parents were genotyped for a 45–base pair deletion/insertion (del/ins) in 3'-untranslated region of exon 8 and for an exon 4 C to T transition.

Results: Eighty-nine children were genotyped for the exon 8 allele: 50 children had del/del, 33 had del/ins, and 6 had ins/ins. Mean (±SD) body mass index (BMI; in kg/m²) was greater for children with del/ins (24.1 ± 5.9) than for children with del/del (20.4 ± 4.8; P < 0.001). BMI of ins/ins children (23.7 ± 7.8) was not significantly different from that of del/ins children. A greater BMI in del/ins children was independent of race and sex. Body composition was also different according to UCP2 genotype. All body circumferences and skinfold thicknesses examined were significantly greater in del/ins than in del/del children. Body fat mass as determined by dual-energy X-ray absorptiometry was also greater in del/ins than in del/del children (P < 0.005). For 104 children genotyped at exon 4, no significant differences in BMI or body composition were found among the 3 exon 4 genotypes. Neither resting energy expenditure nor respiratory quotient were different according to UCP2 exon 4 or exon 8 genotype.

Conclusions: The exon 8 ins/del polymorphism of UCP2 appears to be associated with childhood-onset obesity. The UCP2/UCP3 genetic locus may play a role in childhood body weight.

Key Words: Body mass index • weight • obesity • polymorphism • genetics • childhood

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