Effects of Pro12Ala polymorphism of peroxisome proliferator-activated receptor γ2 gene on rosiglitazone response in type 2 diabetes
Effects of Pro12Ala polymorphism of peroxisome proliferator-activated receptor γ2 gene on rosiglitazone response in type 2 diabetes
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DOI：
10.1016/j.clpt.2005.04.013
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发表时间：
2005-08-01
影响因子：
6.7
通讯作者：
Lee, HC
中科院分区：
文献类型：
--
作者：
Kang, ES;Park, SY;Lee, HC
目的：探讨过氧化物酶体增殖物激活受体(PPAR)γ2基因Pro12Ala多态性对2型糖尿病患者罗格列酮疗效的影响。方法：198例2型糖尿病患者给予罗格列酮(4 mg/d)治疗12周。结果：Ala12等位基因频率为0.04。在198例患者中，183例为Pro12Pro基因，15例为Pro12A1a基因。未发现Ala12A1a基因。携带Ala12等位基因的受试者空腹血糖水平下降幅度明显大于不携带该等位基因的受试者(50.6+/-27.8 mg/dL比24.3+/-41.9 mg/dL，P=0.026)。此外，携带Ala12等位基因的受试者血红蛋白A(1c)水平的下降幅度明显大于不携带该等位基因的受试者(1.41%+/-1.47%对0.57%+/-1.16%，P=.015)。Pro12Pro组和Pro12A1a变异组对罗格列酮的有效率分别为43.72%和86.67%，差异有统计学意义(P=0.002)。结论：PPAR-Gamma 2基因Pro12A1a基因携带者对罗格列酮的疗效优于Pro12Pro基因携带者。PPAR-Gamma 2基因的遗传变异可影响2型糖尿病患者对罗格列酮治疗的反应。
Objective: The aim of this study was to examine the effects of the Pro12Ala polymorphism of the peroxisome proliferator-activated receptor (PPAR) gamma 2 gene on the response to rosiglitazone in patients with type 2 diabetes mellitus.Methods: A total of 198 patients with type 2 diabetes mellitus were treated with rosiglitazone (4 mg/d) for 12 weeks without a change in previous medications. All patients were genotyped for the PPAR gamma 2 Pro12A1a polymorphism.Results: The Ala12 allele frequency was 0.04. Of the 198 patients, 183 had the Pro12Pro genotype and 15 had the Pro12A1a genotype. The Ala12A1a genotype was not observed. The decrease in fasting plasma glucose level was significantly greater in subjects with the Ala12 allele than in those without the allele (50.6 +/- 27.8 mg/dL versus 24.3 +/- 41.9 mg/dL, P = .026). In addition, the decrease in hemoglobin A(1c) level was significantly greater in subjects with the Ala12 allele than in those without the allele (1.41% +/- 1.47% versus 0.57% +/- 1.16%, P = .015). There was a significant difference in the response rate to rosiglitazone treatment between the Pro12Pro group and the Pro12A1a variant group (43.72% versus 86.67%, P = .002).Conclusion: Patients with the Pro12A1a genotype in the PPAR gamma 2 gene had a better therapeutic response to rosiglitazone than did patients with the Pro12Pro genotype. The genetic variations in the PPAR gamma 2 gene can affect the response to rosiglitazone treatment in patients with type 2 diabetes mellitus.