Document Type
Article
Embargo Period
1-1-2024
Publication Date
10-1-1998
Abstract
Human uncoupling protein 3 (UCP3) is a mitochondrial transmembrane carrier that uncouples oxidative ATP phosphorylation. With the capacity to participate in thermogenesis and energy balance, UCP3 is an important obesity candidate gene. A missense polymorphism in exon 3 (V102I) was identified in an obese and diabetic proband. A mutation introducing a stop codon in exon 4 (R143X) and a terminal polymorphism in the splice donor junction of exon 6 were also identified in a compound heterozygote that was morbidly obese and diabetic. Allele frequencies of the exon 3 and exon 6 splice junction polymorphisms were determined and found to be similar in Gullah-speaking African Americans and the Mende tribe of Sierra Leone, but absent in Caucasians. Moreover, in exon 6-splice donor heterozygotes, basal fat oxidation rates were reduced by 50%, and the respiratory quotient was markedly increased compared with wild-type individuals, implicating a role for UCP3 in metabolic fuel partitioning.
Journal
Journal of Clinical Investigation
DOI
doi: 10.1172/JCI4115
Recommended Citation
Argyropoulos, George; Brown, Angela M.; Willi, Steven M.; Zhu, Jianguo; He, Yufang; Reitman, Marc; Gevao, Sahr M.; Spruill, Ida; and Garvey, W. Timothy, "Effects of Mutations in the Human Uncoupling Protein 3 Gene on the Respiratory Quotient and Fat Oxidation in Severe Obesity and Type 2 Diabetes" (1998). MUSC Faculty Journal Articles. 114.
https://medica-musc.researchcommons.org/facarticles/114