Genetic Variance in Uncoupling Protein 2 in Relation to Obesity, Type 2 Diabetes, and Related Metabolic Traits : Focus on the Functional −866G>A Promoter Variant (rs659366)‎

Abstract EN

Uncoupling proteins (UCPs) are mitochondrial proteins able to dissipate the proton gradient of the inner mitochondrial membrane when activated.

This decreases ATP-generation through oxidation of fuels and may theoretically decrease energy expenditure leading to obesity.

Evidence from Ucp(−/−) mice revealed a role of UCP2 in the pancreatic β-cell, because β-cells without UCP2 had increased glucose-stimulated insulin secretion.

Thus, from being a candidate gene for obesity UCP2 became a valid candidate gene for type 2 diabetes mellitus.

This prompted a series of studies of the human UCP2 and UCP3 genes with respect to obesity and diabetes.

Of special interest was a promoter variant of UCP2 situated 866bp upstream of transcription initiation (−866G>A, rs659366).

This variant changes promoter activity and has been associated with obesity and/or type 2 diabetes in several, although not all, studies.

The aim of the current paper is to summarize current evidence of association of UCP2 genetic variation with obesity and type 2 diabetes, with focus on the −866G>A polymorphism.