Variation in the AU(AT)-Rich Element within the 3'-Untranslated Region of PPP1R3 Is Associated with Variation in Plasma Glucose in Aboriginal Canadians

We are investigating associations between variations in candidate genes on chromosome 7q and diabetes-related phenotypes in Cana-dian Oji-Cree. One of these genes encodes the skeletal muscle regu-latory G subunit of the glycogen-associated form of protein phospha-tase 1 (PPPIR3), which may play a key role in muscle glycogen metabolism. There is a common 5-bp insertion-deletion polymor-phism in a messenger ribonucleic acid-stabilizing AU(AT)-rich ele-ment within the 39-untranslated region (UTR) of PPPIR3. The D allele had a frequency of 0.30 in the Oji-Cree. We found that this 39-UTR variation of PPPIR3 was significantly associated with variation in 2-h postprandial glucose in adult Oji-Cree with type 2 diabetes or im-paired glucose tolerance (IGT). Specifically, Oji-Cree with diabetes or IGT who were D/D homozygotes had significantly lower 2-h post-prandial plasma glucose than subjects with the other genotypes.