期刊
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
卷 65, 期 6, 页码 917-926出版社
WILEY-BLACKWELL
DOI: 10.1111/j.1365-2125.2008.03145.x
关键词
C-11377G polymorphism; T45G polymorphism; adiponectin; diplotype; rosiglitazone efficacy; Type 2 diabetes
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). METHODS 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 (4mg 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. RESULTS 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. CONCLUSIONS 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.
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