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

• Published in: Diabetes (New York, N.Y.) Vol. 53; no. 3; pp. 847 - 851
• Main Authors: Shin, Hyoung Doo, Park, Byung Lae, Kim, Lyoung Hyo, Jung, Hye Seung, Cho, Young Min, Moon, Min Kyong, Park, Young Joo, Lee, Hong Kyu, Park, Kyong Soo
• Format: Journal Article
• Language: English
• Published: United States American Diabetes Association 01.03.2004
• Subjects: Aged; Care and treatment; Carrier Proteins; Case studies; Diabetes Mellitus, Type 2 - genetics; Diabetics; Female; Genes, Dominant; Genes, Recessive; Genetic polymorphisms; Genotype; Health aspects; Humans; Introns - genetics; Lipid Metabolism; Lipocalin 1; Male; Middle Aged; Obesity; Obesity - genetics; Peroxisomes; Polymorphism, Genetic; Receptors, Cytoplasmic and Nuclear - genetics; Reference Values; Transcription Factors - genetics; South Korea
• ISSN: 0012-1797; 1939-327X
• DOI: 10.2337/diabetes.53.3.847

Genetic Polymorphisms in Peroxisome Proliferator-Activated Receptor δ Associated With Obesity Hyoung Doo Shin 1 , Byung Lae Park 1 , Lyoung Hyo Kim 1 , Hye Seung Jung 2 3 , Young Min Cho 2 3 , Min Kyong Moon 2 3 , Young Joo Park 2 3 , Hong Kyu Lee 2 3 and Kyong Soo Park 2 3 1 Department of Genetic Epidemiology, SNP Genetics, Seoul, Korea 2 Genome Research Center for Diabetes and Endocrine Disease, Clinical Research Institute, Seoul National University Hospital, Seoul, Korea 3 Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea 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. LD, linkage disequilibrium PPAR, peroxisome proliferator-activated receptor SNP, single nucleotide polymorphism UTR, untranslated region 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. DIABETES