Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University Xiangya School of Medicine, Changsha, Hunan 410078, PR China.
J Clin Pharmacol. 2010 Sep;50(9):1022-30. doi: 10.1177/0091270009355159. Epub 2010 May 24.
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.
目的在于研究过氧化物酶体增殖物激活受体γ共激活因子-1α（PGC-1α） Thr394Thr 和 Gly482Ser 多态性是否会影响中国 2 型糖尿病患者使用罗格列酮的反应。在通过聚合酶链反应-限制性片段长度多态性分析对 241 名患者进行 PGC-1α Thr394Thr 和 Gly482Ser 多态性基因分型的研究中，41 名不同 Thr394Thr 或 Gly482Ser 基因型的患者接受了为期 12 周的口服罗格列酮（4mg/d）治疗。Thr394Thr 的 A 等位基因携带者的高密度脂蛋白胆固醇（HDL-C）升高幅度较小，餐后血清胰岛素水平降低幅度也较小（P<.05），PGC-1α Gly482Gly 的患者空腹血糖降低幅度较大（P<.01），餐后血清胰岛素降低幅度也较大（P<.05）。与 Gly482Ser+Ser482Ser 相比。在接受罗格列酮治疗后，Thr394Thr 的 A 等位基因和 Gly482Ser 的 S 等位基因携带者 GG 有恶化趋势（P<.05），而 Gly/Gly 对罗格列酮有显著的治疗反应（P<.05）。这些数据表明，PGC-1α Thr394Thr 和 Gly482Ser 多态性与中国 2 型糖尿病患者多剂量罗格列酮治疗的疗效有关。
