Polymorphism in the glycogen-associated regulatory subunit of type 1 protein phosphatase (PPP1R3) gene and insulin sensitivity.
Abstract
A polymorphism (PP1ARE) in the 3'-untranslated region of the gene encoding the glycogen-associated regulatory subunit of type 1 protein phosphatase PPP1R3 is associated with insulin resistance in Pima Indians. The aim of this study was to investigate whether two common variants in the PPP1R3 gene, Asp905Tyr and PP1ARE, are associated with reduced insulin sensitivity or can predict the development of impaired glucose tolerance (IGT) or type 2 diabetes during a 20-year follow-up period in 696 50-year-old Caucasian men. The allelic frequency of Tyr905 was 0.11 (95% CI 0.09-0.13) and of PP1ARE 0.34 (0.31-0.37) and the two polymorphisms were in linkage disequilibrium (chi2 = 46, P < 0.0001, Fisher's exact test). None of the polymorphisms was associated with the development of IGT or type 2 diabetes, but the PP1ARE polymorphism was weakly correlated to whole-body insulin sensitivity (r = -0.08, P = 0.04). In conclusion, we found no evidence in Swedish men that the PP1ARE or the Asp905Tyr variants over a 20-year period predict the development of IGT or type 2 diabetes, but the PP1ARE polymorphism could have a higher penetrance in other populations.
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Known genetic mutations associated with insulin resistance are rare in healthy subjects across populations.
“Examination of groups of healthy subjects in a number of different populations has shown that known genetic mutations associated with insulin resistance are rare [20, 39, 40, 41, 42, 43, 44].”
From The relative contributions of insulin resistance and beta-cell dysfunction to the pathophysiology of type 2 diabetes (2003) · cites this paper as [43]
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- Authors
- Hansen, L., Reneland, R., Berglund, L., Rasmussen, S. K., Hansen, T., Lithell, H., & Pedersen, O.
- Affiliations
- Steno Diabetes Center Copenhagen (DK)
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2000-02-01
- Volume
- 49
- Issue
- 2
- Pages
- 298-301
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2051127607
- Cited by
- 22
- References
- 11
- Citations by year
- 2025: 1 · 2024: 1 · 2022: 1 · 2020: 1 · 2018: 2
- FWCI
- 1.75
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Diabetes (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- 3' untranslated region, insulin sensitivity, insulin resistance, impaired glucose tolerance, type 2 diabetes, genetic susceptibility, linkage disequilibrium, Pima Indians, Swedish men
- MeSH terms
- Alleles, Diabetes Mellitus, Type 2, Follow-Up Studies, Gene Frequency, Humans, Insulin Resistance, Genetic Linkage, Longitudinal Studies, Male, Middle Aged, Phosphoprotein Phosphatases, Polymorphism, Genetic, Glucose Intolerance, White People
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