title: PGC-1alpha Gly482Ser polymorphism is associated with the plasma adiponectin level in type 2 diabetic men.
abstract: Peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1alpha) is a multifunctional transcriptional regulator for the pathways controlling mitochondrial biogenesis, oxidative metabolism, and glucose homeostasis. Genetic studies have suggested that Gly482Ser polymorphism of the PGC-1alpha gene is associated with a higher risk of type 2 diabetes, obesity, and hypertension. Adiponectin is an antidiabetic and antiatherogenic adipocytokine that is specifically produced by adipose tissue, and the transcription of the adiponectin gene is regulated by PPARgamma. In this study, we examined the effect of Gly482Ser polymorphism on the plasma adiponectin level in Japanese type 2 diabetics. The Gly482Ser genotype was associated with a lower plasma adiponectin level in type 2 diabetic men, but not in type 2 diabetic women. The impact of this variation on the adiponectin promoter was also assessed by a reporter gene assay, but there was no significant difference between activation by the wild type and Gly482Ser- PGC-1alpha proteins, indicating that this variation itself has no functional effect. Evaluation of the pattern of linkage disequilibrium revealed that the Gly482Ser polymorphism is located in the largest linkage disequilibrium block of the PGC-1alpha gene. Therefore the observed gender-specific association between PGC-1alpha and the plasma adiponectin level may reflect linkage disequilibrium of Gly482Ser polymorphism with other causative variations.
authors.affiliation: Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
authors.forename: Yukiyoshi
authors.initials: Y
authors.lastname: Okauchi
authors.forename: Hiromi
authors.initials: H
authors.lastname: Iwahashi
authors.forename: Kohei
authors.initials: K
authors.lastname: Okita
authors.forename: Ming
authors.initials: M
authors.lastname: Yuan
authors.forename: Morihiro
authors.initials: M
authors.lastname: Matsuda
authors.forename: Toshiya
authors.initials: T
authors.lastname: Tanaka
authors.forename: Junichiro
authors.initials: J
authors.lastname: Miyagawa
authors.forename: Tohru
authors.initials: T
authors.lastname: Funahashi
authors.forename: Yukio
authors.initials: Y
authors.lastname: Horikawa
authors.forename: Iichiro
authors.initials: I
authors.lastname: Shimomura
authors.forename: Kazuya
authors.initials: K
authors.lastname: Yamagata
mesh_terms: D052242:Adiponectin / Q000097:blood; D000368:Aged; D002478:Cells, Cultured; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000235:genetics*; D005260:Female; D005998:Glycine / Q000235:genetics; D006367:HeLa Cells; D006360:Heat-Shock Proteins / Q000235:genetics*; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D020641:Polymorphism, Single Nucleotide; D012694:Serine / Q000235:genetics; D012727:Sex Characteristics; D014157:Transcription Factors / Q000235:genetics*; D014162:Transfection
chemical_list: C499918:ADIPOQ protein, human; D052242:Adiponectin; D006360:Heat-Shock Proteins; C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D014157:Transcription Factors; D012694:Serine; D005998:Glycine