The Common Polymorphisms (Single Nucleotide Polymorphism [SNP] +45 and SNP +276) of the Adiponectin Gene Predict the Conversion From Impaired Glucose Tolerance to Type 2 Diabetes

The STOP-NIDDM Trial

  1. Jelena Zacharova1,
  2. Jean-Louis Chiasson2,
  3. Markku Laakso1 and
  4. the STOP-NIDDM Study Group*
  1. 1Department of Medicine, University of Kuopio, Kuopio, Finland
  2. 2Research Centre, Centre Hospitalier de l’Université de Montréal, Hôtel-Dieu, Department of Medicine, University of Montreal, Quebec, Canada
  1. Address correspondence and reprint requests to Markku Laakso, MD, Professor and Chair, Department of Medicine, University of Kuopio, 70210 Kuopio, Finland. E-mail: markku.laakso{at}kuh.fi

Abstract

Adiponectin is an adipose tissue-specific protein with insulin-sensitizing and antiatherogenic properties. Therefore, the adiponectin gene is a promising candidate gene for type 2 diabetes. We investigated the single nucleotide polymorphisms (SNPs) +45T/G and +276G/T of the adiponectin gene as predictors for the conversion from impaired glucose tolerance to type 2 diabetes in the STOP-NIDDM trial, which aimed to investigate the effect of acarbose compared with placebo on the prevention of type 2 diabetes. Compared with the TT genotype, the G-allele of SNP +45 was associated with a 1.8-fold risk for type 2 diabetes (95% CI 1.12–3.00, P = 0.015) in the placebo group. Subjects treated with placebo and simultaneously having the G-allele of SNP +45 and the T-allele of SNP +276 (the risk genotype combination) had a 4.5-fold (1.78–11.3, P = 0.001) higher risk of developing type 2 diabetes compared with subjects carrying neither of these alleles. Women carrying the risk genotype combination had an especially high risk of conversion to diabetes (odds ratio 22.2, 95% CI 2.7–183.3, P = 0.004). In conclusion, the G-allele of SNP +45 is a predictor for the conversion to type 2 diabetes. Furthermore, the combined effect of SNP +45 and SNP +276 on the development of type 2 diabetes was stronger than that of each SNP alone.

Footnotes

  • *

    * Members of the STOP-NIDDM Study Group have been listed previously (Lancet 359:2072–2077, 2002).

    • Accepted December 13, 2004.
    • Received August 9, 2004.
« Previous | Next Article »Table of Contents