Sun Hong, Gong Zhi-Cheng, Yin Ji-Ye, Liu Hai-Ling, Liu Ying-Zi, Guo Zhi-Wei, Zhou Hong-Hao, Wu Jing, Liu Zhao-Qian
Department of Pharmacy, Fujian Provincal Hospital, Fuzhou, China.
Br J Clin Pharmacol. 2008 Jun;65(6):917-26. doi: 10.1111/j.1365-2125.2008.03145.x. Epub 2008 Apr 22.
Rosiglitazone is able to increase serum adiponectin levels significantly in Type 2 diabetic patients. :The role of genetic factors that determine the marked interindividual variability in glucose-lowering efficacy of rosiglitazone in Chinese patients is not known. The current study was designed to evaluate the impact of the adiponectin common allele 45T/G and -11377C/G polymorphisms on the response to rosiglitazone monotherapy in Chinese patients with Type 2 diabetes (T2D).
The genetic polymorphisms of adiponectin alleles 45T/G and -11377C/G as well as their common diplotypes are significantly associated with an attenuated fasting plasma glucose, postprandial plasma glucose and homeostasis model assessment for insulin resistance as well as an enhanced adiponectin concentration in Chinese patients with T2D after rosiglitazone treatment. AIMS The aim of the present study was to evaluate the impact of adiponectin allele T45G and C-11377G genetic polymorphisms on efficacy of rosiglitazone in Chinese patients with type 2 diabetes (T2D).
Patients with T2D (n = 255) and 120 healthy volunteers were enrolled to identify 45T/G and -11377C/G genotypes by polymerase chain reaction-restriction fragment length polymorphism assay. Forty-two T2D patients with different 45T/G or -11377C/G genotypes received orally rosiglitazone as a single-dose therapy (4 mg day-1 p.o.) for 12 weeks. Serum triglyceride, fasting plasma glucose (FPG), postprandial plasma glucose (PPG), glycated hemoglobin, fasting serum insulin, postprandial serum insulin, total cholesterol, homeostasis model assessment for insulin resistance (HOMA-IR), low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol (HDL-c) and adiponectin concentration were determined before and after rosiglitazone treatment.
We showed an attenuated rosiglitazone effect in patients with -11377CG+GG heterozygote genotype on FPG, PPG, HOMA-IR compared with -11377CC homozygote genotype. However, we found an enhanced rosiglitazone effect on serum adiponectin concentration in patients with -11377CC homozygote genotype compared with -11377CG+GG heterozygote genotype (P = 0.000) and in patients with 45TG + GG heterozygote genotype compared with 45TT homozygote genotype (P = 0.018). Finally, our results showed that there was an enhanced effect in patients with -11377/45 CGTT diplotype compared with other discovered diplotypes on FPG (P = 0.001) and PPG (P = 0.003) after rosiglitazone treatment.
These data suggest that the adiponectin allele 45T/G and -11377C/G polymorphisms are significantly associated with the therapeutic efficacy of multiple-dose rosiglitazone in Chinese patients with T2D.
罗格列酮能够显著提高2型糖尿病患者血清脂联素水平。：决定罗格列酮在中国患者中降糖疗效存在显著个体差异的遗传因素的作用尚不清楚。本研究旨在评估脂联素常见等位基因45T/G和-11377C/G多态性对中国2型糖尿病（T2D）患者罗格列酮单药治疗反应的影响。
脂联素等位基因45T/G和-11377C/G的基因多态性及其常见单倍型与罗格列酮治疗后中国T2D患者空腹血糖、餐后血糖和胰岛素抵抗稳态模型评估的降低以及脂联素浓度的升高显著相关。目的本研究的目的是评估脂联素等位基因T45G和C-11377G基因多态性对中国2型糖尿病（T2D）患者罗格列酮疗效的影响。
纳入255例T2D患者和120名健康志愿者，通过聚合酶链反应-限制性片段长度多态性分析确定45T/G和-11377C/G基因型。42例具有不同45T/G或-11377C/G基因型的T2D患者接受口服罗格列酮单剂量治疗（4mg/天，口服），持续12周。在罗格列酮治疗前后测定血清甘油三酯、空腹血糖（FPG）、餐后血糖（PPG）、糖化血红蛋白、空腹血清胰岛素、餐后血清胰岛素、总胆固醇、胰岛素抵抗稳态模型评估（HOMA-IR）、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇（HDL-c）和脂联素浓度。
我们发现，与-11377CC纯合子基因型相比，-11377CG+GG杂合子基因型患者的罗格列酮对FPG、PPG、HOMA-IR的作用减弱。然而，我们发现，与-11377CG+GG杂合子基因型患者相比，-11377CC纯合子基因型患者罗格列酮对血清脂联素浓度的作用增强（P=0.000），与45TT纯合子基因型患者相比，45TG+GG杂合子基因型患者罗格列酮对血清脂联素浓度的作用增强（P=0.018）。最后，我们的结果显示，与其他发现的单倍型相比，-11377/45 CGTT单倍型患者在罗格列酮治疗后FPG（P=0.001）和PPG（P=0.003）方面的作用增强。
这些数据表明，脂联素等位基因45T/G和-11377C/G多态性与多剂量罗格列酮在中国T2D患者中的治疗疗效显著相关。
