Effects of the peroxisome proliferator activated receptor-γ coactivator-1α (PGC-1α) Thr394Thr and Gly482Ser polymorphisms on rosiglitazone response in Chinese patients with type 2 diabetes mellitus.

The objective was to investigate whether peroxisome proliferator activated receptor-γ coactivator-1α (PGC-1α) Thr394Thr and Gly482Ser polymorphisms influence rosiglitazone response in Chinese patients with type 2 diabetes mellitus. Among the 241 patients enrolled in genotyping for PGC-1α Thr394Thr and Gly482Ser polymorphisms by polymerase chain reaction-restriction fragment length polymorphism assay, 41 patients with different Thr394Thr or Gly482Ser genotypes received oral rosiglitazone (4 mg/d) for 12 consecutive weeks. Carriers of A allele of Thr394Thr had high density lipoprotein-cholesterol that was enhanced to a lesser degree and smaller attenuated postprandial serum insulin compared with G alleles (P < .05), and patients with PGC-1α Gly482Gly had fasting plasma glucose that was attenuated to a greater degree (P < .01) and postprandial serum insulin (P < .05) compared with Gly482Ser+Ser482Ser. After rosiglitazone treatment, carriers of A allele of Thr394Thr and Ser allele of Gly482Ser showed a trend in worsening for GG (P < .05) and a significant therapeutic response to rosiglitazone for Gly/Gly (P < .05). These data suggest that the PGC-1α Thr394Thr and Gly482Ser polymorphisms are associated with therapeutic efficacy of multiple-dose rosiglitazone in Chinese patients with type 2 diabetes mellitus.