Genetic Polymorphisms in Peroxisome Proliferator-Activated Receptor δ Associated With Obesity

  1. Hyoung Doo Shin1,
  2. Byung Lae Park1,
  3. Lyoung Hyo Kim1,
  4. Hye Seung Jung23,
  5. Young Min Cho23,
  6. Min Kyong Moon23,
  7. Young Joo Park23,
  8. Hong Kyu Lee23 and
  9. Kyong Soo Park23
  1. 1Department of Genetic Epidemiology, SNP Genetics, Seoul, Korea
  2. 2Genome Research Center for Diabetes and Endocrine Disease, Clinical Research Institute, Seoul National University Hospital, Seoul, Korea
  3. 3Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
  1. Address correspondence and reprint requests to Prof. K.S. Park, Department of Internal Medicine, Seoul National University College of Medicine, 28 Yongon-Dong, Chongno-Gu, Seoul, Korea 110-744. E-mail: kspark{at}snu.ac.kr

Abstract

Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors regulating the expression of genes involved in lipid and glucose metabolism. Three different PPARs, PPAR-α, -γ, and -δ, have been characterized, and they are distinguished from each other by tissue distribution and cell activation. All PPARs are, to different extents, activated by fatty acids and derivatives. Recently, it has been shown that PPAR-δ serves as a widespread regulator of fat burning, suggesting that it might be a potential target in the treatment of obesity and type 2 diabetes. In an effort to identify polymorphic markers in potential candidate genes for type 2 diabetes, we have sequenced PPAR-δ, including −1,500 bp of the 5′ flanking region. Nine polymorphisms were identified in PPAR-δ: four in the intron, one in the 5′ untranslated region (UTR), and four in the 3′ UTR. Among identified polymorphisms, five common sites, including c.−13454G>T, c.−87T>C, c.2022+12G>A, c.2629T>C, and c.2806C>G, were genotyped in subjects with type 2 diabetes and normal control subjects (n = 702). The genetic associations with the risk of type 2 diabetes and metabolic phenotype were analyzed. No significant associations with the risk of type 2 diabetes were detected. However, several positive associations of PPAR-δ polymorphisms with fasting plasma glucose and BMI were detected in nondiabetic control subjects. The genetic information about PPAR-δ from this study would be useful for further genetic study of obesity, diabetes, and other metabolic diseases.

Footnotes

  • Additional information for this article can be found in an online data supplement at http://diabetes.diabetesjournals.org.

    • Accepted November 24, 2003.
    • Received September 2, 2003.
| Table of Contents