Variation in the AU(AT)-rich element within the 3'-untranslated region of PPP1R3 is associated with variation in plasma glucose in aboriginal Canadians

J Clin Endocrinol Metab. 1998 Nov;83(11):3980-3. doi: 10.1210/jcem.83.11.5219.

Abstract

We are investigating associations between variations in candidate genes on chromosome 7q and diabetes-related phenotypes in Canadian Oji-Cree. One of these genes encodes the skeletal muscle regulatory G subunit of the glycogen-associated form of protein phosphatase 1 (PPPIR3), which may play a key role in muscle glycogen metabolism. There is a common 5-bp insertion-deletion polymorphism in a messenger ribonucleic acid-stabilizing AU(AT)-rich element within the 3'-untranslated region (UTR) of PPPIR3. The D allele had a frequency of 0.30 in the Oji-Cree. We found that this 3'-UTR variation of PPPIR3 was significantly associated with variation in 2-h postprandial glucose in adult Oji-Cree with type 2 diabetes or impaired glucose tolerance (IGT). Specifically, Oji-Cree with diabetes or IGT who were D/D homozygotes had significantly lower 2-h postprandial plasma glucose than subjects with the other genotypes. There was no association of the PPPIR3 genotype either with the presence of type 2 diabetes or IGT or with other quantitative traits in this sample. These findings suggest that common PPPIR3 3'-UTR variation that potentially affects messenger ribonucleic acid stability is associated with variation in glycemia in Oji-Cree subjects with type 2 diabetes.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 3' Untranslated Regions*
  • Alleles
  • American Native Continental Ancestry Group / genetics*
  • Base Pairing*
  • Blood Glucose / metabolism*
  • Chromosomes, Human, Pair 7
  • Diabetes Mellitus, Type 2 / genetics
  • Genetic Variation*
  • Genotype
  • Humans
  • Ontario
  • Phenotype
  • Phosphoprotein Phosphatases / genetics*
  • Protein Phosphatase 1
  • Sequence Analysis, DNA

Substances

  • 3' Untranslated Regions
  • Blood Glucose
  • PPP1R3A protein, human
  • Phosphoprotein Phosphatases
  • Protein Phosphatase 1