Demonstration of a new genotype encoding uncoupling protein 2 and association with obesity

Abstract

    Uncoupling protein 2 (UCP2), mapped to chromosome 11q13 in humans, plays an important role in energy metabolism and body weight regulation. Some positive results have been reported for associations of obesity and diabetes in Caucasians with the polymorphism of the UCP2 gene in the 3'-untranslated region (3' UTR) of exon 8 (insertion and deletion types). We examined the genotypes of adult men in Aomori Prefecture situated in northern Japan, in order to investigate associations between the polymorphism and obesity. In the present study, in addition to the insertion type of 457 bp, a new genotype composed of 502 bp was detected, while the deletion type of 412 bp was not. Although the sequence of inserted 45 bp in the 457 bp type was entirely identical to that reported previously, the fragment was inserted at the 111 bp from the 3' end of the exon 8. In the 502 bp type, the same fragment was further added to the 457 bp type. The new genotype was observed in 4 of 18 subjects as the 457/502 heterozygote and other subjects were the 457/457 homozygote.
    Significant associations were found between the polymorphism of UCP2 gene and obesity in adult Japanese men. Weight, thicknesses of the subcutaneous adipose tissues at triceps and lateral abdomen, fat percentage and fatmass were significantly higher (p < 0.05) in subjects with the heterozygote (457/502) than in subjects with the homozygote (457/457). These results suggest that a new genotype (502 bp) is involved in obesity.