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.
Zhang
Ke-Han
KH
Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University Xiangya School of Medicine, Changsha, Hunan 410078, PR China.
Huang
Qiong
Q
Dai
Xing-Ping
XP
Yin
Ji-Ye
JY
Zhang
Wei
W
Zhou
Gan
G
Zhou
Hong-Hao
HH
Liu
Zhao-Qian
ZQ
D000328:Adult; D000483:Alleles; D044466:Asian People; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000235:genetics*; D005260:Female; D005838:Genotype; D006360:Heat-Shock Proteins / Q000235:genetics / Q000627:therapeutic use*; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000235:genetics / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D047495:PPAR gamma / Q000235:genetics / Q000627:therapeutic use*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D019518:Postprandial Period / Q000235:genetics; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000627:therapeutic use*; D014157:Transcription Factors / Q000235:genetics / Q000627:therapeutic use*
D006360:Heat-Shock Proteins; D007004:Hypoglycemic Agents; D007328:Insulin; D047495:PPAR gamma; C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D045162:Thiazolidinediones; D014157:Transcription Factors; D000077154:Rosiglitazone