Pgc-1α Gly482ser Polymorphism Is Associated With The Plasma Adiponectin Level In Type 2 Diabetic Men

摘要

Peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-lα) 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-lα 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 PPARγ. 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-lα 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-lα gene. Therefore the observed gender-specific association between PGC-lα and the plasma adiponectin level may reflect linkage disequilibrium of Gly482Ser polymorphism with other causative variations.