Genetic polymorphisms in peroxisome proliferator-activated receptor delta associated with obesity.
Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors regulating the expression of genes involved in lipid and glucose metabolism. Three different PPARs, PPAR-alpha, -gamma, and -delta, 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-delta 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-delta, including -1,500 bp of the 5' flanking region. Nine polymorphisms were identified in PPAR-delta: 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-delta polymorphisms with fasting plasma glucose and BMI were detected in nondiabetic control subjects. The genetic information about PPAR-delta from this study would be useful for further genetic study of obesity, diabetes, and other metabolic diseases.
Department of Genetic Epidemiology, SNP Genetics, Seoul, Korea.
Hyoung Doo
HD
Shin
Byung Lae
BL
Park
Lyoung Hyo
LH
Kim
Hye Seung
HS
Jung
Young Min
YM
Cho
Min Kyong
MK
Moon
Young Joo
YJ
Park
Hong Kyu
HK
Lee
Kyong Soo
KS
Park
D000368:Aged; D002352:Carrier Proteins; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics; D005260:Female; D005799:Genes, Dominant; D005808:Genes, Recessive; D005838:Genotype; D006801:Humans; D007438:Introns / Q000235:genetics; D050356:Lipid Metabolism; D054835:Lipocalin 1; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000235:genetics*; D011110:Polymorphism, Genetic; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics*; D012016:Reference Values; D014157:Transcription Factors / Q000235:genetics*
D002352:Carrier Proteins; C518443:LCN1 protein, human; D054835:Lipocalin 1; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors