Analysis of the relationship between the pro12Ala variant in the PPAR-γ2 gene and the response rate to therapy with pioglitazone in patients with type 2 diabetes
Analysis of the relationship between the pro12Ala variant in the PPAR-γ2 gene and the response rate to therapy with pioglitazone in patients with type 2 diabetes
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DOI：
10.2337/diacare.26.3.825
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发表时间：
2003-03-01
期刊：
影响因子：
16.2
通讯作者：
Paschke, R
中科院分区：
文献类型：
--
作者：
Blüher, M;Lübben, GR;Paschke, R
目的-研究过氧化物酶体增殖物激活受体-γ研究设计和方法-共有131名患者在一项开放标签、随机、吡格列酮（45 mg o.d.）的多中心研究在大于或等于26周的过程中。对吡格列酮治疗的反应定义为吡格列酮治疗26周后空腹血糖降低> 20%或HbA（1c）值降低> 15%。我们评估了PPAR-gamma基因型和吡格列酮治疗反应率之间的关联。结果-PPAR-gamma基因中的Pro12Ala和Pro12Pro变体与2型糖尿病患者吡格列酮治疗反应率无关。然而，我们发现初始空腹血糖水平> 11.0 mmol/l、HbA（1c）值> 9.0%、BMI> 32 kg/m2和基线空腹C肽浓度> 2.5 pmol/l是吡格列酮治疗应答频率的主要混杂因素。这表明药物治疗反应不依赖于PPAR-γ及其配体吡格列酮之间的药物遗传学效应。Ala12Ala基因型是否在TZD治疗的反应率中起作用仍有待确定。
OBJECTIVE - To investigate the influence of peroxisome proliferator-activated receptor-gamma (PPAR-gamma) gene variants on the response rate to therapy with the thiazolidinedione (TZD) pioglitazone, because in vitro studies have suggested that genetic variants of the PPAR-gamma gene may influence the drug efficacy of TZD.RESEARCH DESIGN AND METHODS - A total of 131 patients were treated in an open-label, randomized, multicenter study with pioglitazone (45 mg o.d.) during a course of greater than or equal to26 weeks. Response to the pioglitazone therapy was defined by either a >20% decrease in fasting plasma glucose or a >15% decrease in HbA(1c) values after 26 weeks of pioglitazone treatment. We evaluated the association between the PPAR-gamma genotype and the response rate to pioglitazone treatment.RESULTS - The Pro12Ala and the Pro12Pro variants in the PPAR-gamma gene are not associated with the response rate to pioglitazone treatment in patients with type 2 diabetes. However, we identified initial fasting plasma glucose level >11.0 mmol/l, HbA(1c) value >9.0%, BMI >32 kg/m(2), and fasting C-peptide concentrations at baseline >2.5 pmol/l as predominant confounding factors for the responder frequency to pioglitazone treatment.CONCLUSIONS - The Pro12Ala variant in the PPAR-gamma gene does not affect the therapy efficacy of pioglitazone, suggesting that the drug-treatment response is independent from pharmacogenetic effects between PPAR-gamma and its ligand pioglitazone. Whether the Ala12Ala genotype plays a role in the response rate to TZD therapy remains to be determined.