Identification of the ENPP1 three-allele risk haplotype and its possible contribution to the development of obesity and insulin resistance in 8-18-year-old learners in communities of the Western Cape, South Africa

Abstract

The ENPP1 (nucleotide pyrophosphatase/phosphodiesterase-1) gene encodes a membrane-bound glycoprotein that inhibits the insulin receptor tyrosine kinase activity, resulting in reduced insulin sensitivity. There has been strong evidence from several previous studies that a common coding variant of ENPP1 (K121Q) and a three-marker haplotype (Q121, IVS20delT-11 and G + 1044TGA) are associated with a higher risk of glucose intolerance and type 2 diabetes as well as childhood obesity. Many different studies attempted to confirm the association in different population groups, but results have been controversial.