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

Hyoung Doo Shin, Byung Lae Park, Lyoung Hyo Kim, Hye Seung Jung, Young Min Cho, Min Kyong Moon, Young Joo Park, Hong Kyu Lee, Kyong Soo Park

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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.

Original languageEnglish
Pages (from-to)847-851
Number of pages5
JournalDiabetes
Volume53
Issue number3
DOIs
StatePublished - 1 Mar 2004

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