Protein targeting to glycogen/PPP1R5: screening of coding and flanking genomic regions for polymorphisms and association analysis with insulin action in Pima Indians.
Insulin resistance, a major predictor of type 2 diabetes mellitus, is genetically inherited in Pima Indians, a population with a high prevalence of the metabolically complex disease. Protein targeting to glycogen/PPP1R5 has recently been identified as a potential regulator of glycogen synthase, the rate-limiting enzyme of the insulin-induced glycogenesis. The gene is located on chromosome 10q23-24, where there is a suggestive linkage to insulin action in this population, establishing it as a functional and positional candidate gene. In this study, we discovered 2 novel polymorphisms upstream of the 5'UTR of the gene, with only one found in Pima Indians, but no polymorphism in the coding sequence. The genotype frequencies of the polymorphism and transcript levels of the gene in skeletal muscle do not correlate with insulin action in the subjects. These results exclude any significant role of protein targeting to glycogen/PPP1R5 in insulin resistance in Pima Indians.
Permana
P A
PA
Phoenix Epidemiology and Clinical Research Branch, National Institutes of Health, Phoenix, Arizona, 85016, USA. ppermana@phx.niddk.nih.gov
Luczy-Bachman
G
G
Bogardus
C
C
D020121:5' Untranslated Regions; D001483:Base Sequence; D002352:Carrier Proteins; D017931:DNA Primers; D018076:DNA, Complementary; D006003:Glycogen / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007198:Indians, North American; D007328:Insulin / Q000502:physiology*; D007333:Insulin Resistance / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins; D007438:Introns; D010749:Phosphoprotein Phosphatases / Q000235:genetics / Q000378:metabolism*; D011110:Polymorphism, Genetic; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
D020121:5' Untranslated Regions; D002352:Carrier Proteins; D017931:DNA Primers; D018076:DNA, Complementary; D007328:Insulin; D047908:Intracellular Signaling Peptides and Proteins; C491294:PPP1R3C protein, human; D012333:RNA, Messenger; D006003:Glycogen; D010749:Phosphoprotein Phosphatases