title: Variation in the AU(AT)-rich element within the 3'-untranslated region of PPP1R3 is associated with variation in plasma glucose in aboriginal Canadians.
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.
authors.affiliation: Robarts Research Institute and Department of Medicine, University of Western Ontario, London, Canada.
authors.forename: R A
authors.initials: RA
authors.lastname: Hegele
authors.forename: S B
authors.initials: SB
authors.lastname: Harris
authors.forename: B
authors.initials: B
authors.lastname: Zinman
authors.forename: J
authors.initials: J
authors.lastname: Wang
authors.forename: H
authors.initials: H
authors.lastname: Cao
authors.forename: A J
authors.initials: AJ
authors.lastname: Hanley
authors.forename: L C
authors.initials: LC
authors.lastname: Tsui
authors.forename: S W
authors.initials: SW
authors.lastname: Scherer
mesh_terms: D020413:3' Untranslated Regions; D000483:Alleles; D044467:American Indian or Alaska Native / Q000235:genetics*; D020029:Base Pairing; D001786:Blood Glucose / Q000378:metabolism*; D002897:Chromosomes, Human, Pair 7; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D009864:Ontario; D010641:Phenotype; D010749:Phosphoprotein Phosphatases / Q000235:genetics*; D054645:Protein Phosphatase 1; D017422:Sequence Analysis, DNA
chemical_list: D020413:3' Untranslated Regions; D001786:Blood Glucose; C114205:PPP1R3A protein, human; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1