The common -866G/A polymorphism in the promoter region of the UCP-2 gene is associated with reduced risk of type 2 diabetes in Caucasians from Italy

J Clin Endocrinol Metab. 2005 Feb;90(2):1176-80. doi: 10.1210/jc.2004-1072. Epub 2004 Nov 23.


Uncoupling protein-2 (UCP2) regulates insulin secretion and may play an important role in linking obesity to type 2 diabetes (T2D). Previous studies of the role of the UCP2 promoter -866G/A single nucleotide polymorphisms (SNP) in T2D have given opposite results. We tested the distribution of the -866G/A SNP in 746 T2D patients and 327 healthy unrelated Caucasians from Italy. We also tested for an effect of the P12A variant of the peroxisomal proliferator-activated receptor-gamma 2 (PPAR gamma 2) gene on diabetes risk given by the UCP2 SNP. Compared with -866G/G carriers, a progressively reduced (P = 0.01) risk of T2D was observed in -866G/A and -866A/A subjects, with the latter showing an approximately 50% risk reduction [odd ratio (OR), 0.51; 95% confidence interval (CI), 0.3-0.8; P = 0.003]. Conversely, the -866G/G genotype was associated with increased risk (OR, 1.31; 95% CI, 1.01-1.71). Overall, the population risk attributable to the UCP2 -866G/G genotype was about 12%. After stratifying for the PPAR gamma 2 polymorphism, the increased risk conferred by the UCP2 G/G genotype was still evident among P12/P12 homozygous subjects (n = 801; OR, 1.38; 95% CI, 1.04-1.83), but seemed to disappear among the X12/A12 subjects (i.e. P12/A12 heterozygous or A12/A12 homozygous subjects; n = 137; OR, 0.87; 95% CI, 0.40-1.91). Whether this apparent difference is entirely due to the different number of carriers of the two PPAR gamma 2 genotypes is a likely possibility that deserves deeper investigation. In conclusion, in our population, the -866G/A SNP is associated with T2D. Additional studies in larger samples are needed to investigate the possibility of a concomitant effect of modifier genes such as PPAR gamma 2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenine
  • Adult
  • Aged
  • Diabetes Mellitus, Type 2 / epidemiology
  • Diabetes Mellitus, Type 2 / genetics*
  • Female
  • Guanine
  • Humans
  • Ion Channels
  • Italy
  • Male
  • Membrane Transport Proteins / genetics*
  • Middle Aged
  • Mitochondrial Proteins / genetics*
  • Polymorphism, Single Nucleotide / genetics*
  • Promoter Regions, Genetic
  • Risk Factors
  • Uncoupling Protein 2
  • White People


  • Ion Channels
  • Membrane Transport Proteins
  • Mitochondrial Proteins
  • UCP2 protein, human
  • Uncoupling Protein 2
  • Guanine
  • Adenine