脂联素基因启动子-11377(C/G)基因多态性与中国2型糖尿病和罗格列酮降糖疗效的相关性研究

Association of adiponectin allele-11377(C/G) polymorphism with type 2 diabetes and rosiglitazone response in Chinese patients

目的:探讨脂联素基因SNP-11377(C/G)与中国汉族2型糖尿病(T2D)的关系及对罗格列酮降糖疗效的影响。方法:应用PCR-RFLP方法对255名T2D和120名健康对照者进行-11377(C/G)基因分型,选取42个不同基因型的T2D患者每天早饭时口服罗格列酮4mg,连续服药12周。测定用药前后的TG、空腹血糖(FPG)、餐后血糖(PPG)、糖化血红蛋白(HbAlc)、空腹胰岛素(FINS)、餐后胰岛素(PINS)、TC、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、胰岛素抵抗指数(HOMA-IR)和脂联素水平。结果:T2D组SNP-11377等位基因频率与基因型频率明显高于健康对照组(P<0.05),并且随着G等位基因的增加,患者的脂联素水平(P<0.01)明显降低,FINS(P<0.05)和HOMA-IR水平(P<0.05)明显增高。在服用罗格列酮后,CC型FPG、PPG和HOMA-IR的降低幅度明显高于突变型(CG+GG)(P<0.05),而CC型脂联素升高幅度明显高于突变型(P<0.01)。结论:脂联素基因启动子-11377C/G遗传变异与胰岛素抵抗和T2D有关,并且可能影响罗格列酮的降糖疗效。

AIM. To evaluate the impact of adiponectin allele 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-11377C/G genotypes by polymerase chain reaction restriction fragment length polymorphism assay. Forty two T2D patients with different-11377C/G genotypes received orally rosiglitazone as a single-dose therapy （4 mg day 1 p. o. ） for 12 weeks. The serum triglyceride, fasting plasma glucose （FPG）, postprandial plasma glucose （PPG）, giycated hemoglobin（HbAic）, fasting serum insulin（FINS）, postprandial serum insu lin （ PINS）, total cholesterol （ TC）, low-density lipoprotein-cholesterol （ LDL-C ）, high-density lipoprotein-cholesterol （ HDI. C）, homeostasis model assessment for insulin resistance （HOMA-IR）, and adiponectin concentration were de termined before and after rosiglitazone treatment. RESULTS：Compared with the health con trol group, the allele frequency of-11377（C/G） and the genotypic frequency were increased in T2D group（P〈0.05）, and as the G allele gene increased, the adiponectin level was significantly decreased,and the levels of FINS and HOMA-IR were significantly increased in T2D patients（P〈0.05）. After treated with rosiglitazone, the de gree of the decrease of the FPG （P〈0.01）, PPG （P〈0.05） and HOMA IR （P〈0.05） levels in the CC genotype was significant higher than that in the other genotypes. However, the degree of the increase of the serum adiponectin concentration（P〈0.01） in the CC genotype was significantly higher than that in the other genotypes. CONCLUSION. These data suggest that the adiponectin allele-11377C/G polymorphisms significantly associated with the pathogenesis of T2D,insulin resistance, and the therapeutic efficacy of rosiglitazone in Chinese patients with T2D.