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PMID: 15592662 Published · ppublish English Journal Article Multicenter Study Research Support, Non-U.S. Gov't

Common polymorphisms of the PPAR-gamma2 (Pro12Ala) and PGC-1alpha (Gly482Ser) genes are associated with the conversion from impaired glucose tolerance to type 2 diabetes in the STOP-NIDDM trial.

Diabetologia ·Vol. 47 ·No. 12 ·2004-12-00 ·Pages 2176-84

Andrulionytè L, Zacharova J, Chiasson JL, Laakso M, STOP-NIDDM Study Group

Abstract

We investigated the effects of the common polymorphisms in the peroxisome proliferator-activated receptor gamma2 (PPAR-gamma2; Pro12Ala) and in PPAR-gamma coactivator 1alpha (PGC-1alpha; Gly482Ser) genes on the conversion from impaired glucose tolerance to type 2 diabetes in participants in the STOP-NIDDM trial. This trial aimed to study the effect of acarbose in the prevention of type 2 diabetes. Genotyping was performed in 770 study subjects whose DNA was available. The Gly482Ser variant in the PGC-1alpha gene was determined with the polymerase chain reaction amplification, Hpa II enzyme digestion, and gel electrophoresis. The Pro12Ala polymorphism of the PPAR-gamma2 gene was determined by the polymerase chain reaction-single-strand conformation polymorphism analysis. The Pro12Pro genotype of the PPAR-gamma2 gene predicted the conversion to diabetes in women in the acarbose group (odds ratio 2.89, 95% CI 1.20 to 6.96; p=0.018). The 482Ser allele of the PGC-1alpha gene had a significant interaction with the mode of treatment (p=0.012), and in the placebo group the 482Ser allele was associated with a 1.6-fold higher risk for type 2 diabetes compared to the Gly482Gly genotype (95% CI 1.06 to 2.33; p=0.023). Acarbose prevented the development of diabetes independently of the genotype of the PPAR-gamma2 gene, but only the carriers of the 482Ser allele of the PGC-1alpha gene were responsive to acarbose treatment. We conclude that the Pro12Pro genotype of the PPAR-gamma2 gene and the 482Ser allele of the PGC-1alpha gene are associated with the conversion from impaired glucose tolerance to type 2 diabetes in the STOP-NIDDM trial.

MeSH Terms
Acarbose/therapeutic use Amino Acid Substitution Diabetes Mellitus, Type 2/drug therapy,genetics Female Glucose Intolerance/genetics Heat-Shock Proteins/genetics Humans Hypoglycemic Agents/therapeutic use Male Middle Aged PPAR gamma/genetics Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha Polymorphism, Single Nucleotide Transcription Factors/genetics
Chemicals
Heat-Shock Proteins Hypoglycemic Agents PPAR gamma PPARGC1A protein, human Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha Transcription Factors Acarbose
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Andrulionytè L
Department of Medicine, University of Kuopio, 70210, Kuopio, Finland.
Zacharova J
Chiasson J-L
Laakso M
STOP-NIDDM Study Group
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Article Info
Journal
Diabetologia
Abbr.
Diabetologia
ISSN
0012-186X
DOI
10.1007/s00125-004-1577-2
Published
2004-12-00
Epub
2004-00-08
Pages
2176-84
Language
English
Region
Germany
NLM ID
0006777
Subset
IM
External Links
PubMed source DOI: 10.1007/s00125-004-1577-2 View journal details
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