PGC-1α Gly482Ser Polymorphism Is Associated with the Plasma Adiponectin Level in Type 2 Diabetic Men

Peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1 alpha) 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-1 alpha 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 PPAR gamma. 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,I reporter gene assay, bill there was no significant difference between activation by the wild type and Gly482Ser- PGC-1 alpha 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-1 alpha gene. Therefore the observed gender-specific association between PGC-1 alpha and the plasma adiponectin level may reflect linkage disequilibrium of Gly482Ser polymorphism with other causative variations.