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.

Abstract

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.

• Authors: Ke-Han Zhang, Qiong Huang, Xing-Ping Dai, Ji-Ye Yin, Wei Zhang, Gan Zhou, Hong-Hao Zhou, Zhao-Qian Liu
• Journal: Journal of clinical pharmacology (J Clin Pharmacol) Vol. 50 Issue 9 Pg. 1022-30 (Sep 2010) ISSN: 1552-4604 [Electronic] England
• PMID: 20498286 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Heat-Shock Proteins
• Hypoglycemic Agents
• Insulin
• PPAR gamma
• PPARGC1A protein, human
• Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
• Thiazolidinediones
• Transcription Factors
• Rosiglitazone

Topics

• Adult
• Alleles
• Asian People
• Diabetes Mellitus, Type 2 (drug therapy, genetics)
• Female
• Genotype
• Heat-Shock Proteins (genetics, therapeutic use)
• Humans
• Hypoglycemic Agents (therapeutic use)
• Insulin (genetics, therapeutic use)
• Male
• Middle Aged
• PPAR gamma (genetics, therapeutic use)
• Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
• Polymorphism, Genetic
• Polymorphism, Restriction Fragment Length
• Postprandial Period (genetics)
• Rosiglitazone
• Thiazolidinediones (therapeutic use)
• Transcription Factors (genetics, therapeutic use)