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 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.
Hegele
R A
RA
Robarts Research Institute and Department of Medicine, University of Western Ontario, London, Canada.
Harris
S B
SB
Zinman
B
B
Wang
J
J
Cao
H
H
Hanley
A J
AJ
Tsui
L C
LC
Scherer
S W
SW
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
D020413:3' Untranslated Regions; D001786:Blood Glucose; C114205:PPP1R3A protein, human; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1