Common polymorphisms of the peroxisome proliferator-activated receptor–γ (Pro12Ala) and peroxisome proliferator-activated receptor–γ coactivator–1 (Gly482Ser) and the response to pioglitazone in Chinese patients with type 2 diabetes mellitus

吡格列酮 内科学 过氧化物酶体增殖物激活受体 内分泌学 2型糖尿病 2型糖尿病 糖尿病 医学 辅活化剂 多态性(计算机科学) 等位基因 受体 生物 基因 遗传学 转录因子
作者
Ming‐Chia Hsieh,Kun‐Der Lin,Kai‐Jen Tien,Shih‐Te Tu,Jeng-Yueh Hsiao,Shun‐Jen Chang,Shiu‐Ru Lin,Shih-Jang Shing,Hung‐Chun Chen
出处
期刊:Metabolism-clinical and Experimental [Elsevier]
卷期号:59 (8): 1139-1144 被引量:52
标识
DOI:10.1016/j.metabol.2009.10.030
摘要

We investigated the effects of the common polymorphisms in the peroxisome proliferator-activated receptor-gamma (PPAR-gamma; Pro12Ala) and in PPAR-gamma coactivator-1(PGC-1; Gly482Ser) genes on the response to pioglitazone in Chinese with type 2 diabetes mellitus. A total of 250 patients with type 2 diabetes mellitus were treated with pioglitazone (30 mg/d) for 24 weeks without a change in previous medications. All patients were genotyped for the PPAR-gamma Pro12Ala and PGC-1 Gly482Ser polymorphisms. The Ala12Ala and Pro12Ala genotypes (26.0% vs 13.5%, P = .025) and Ala allele (15.6% vs 7.3%, P = .008) were significantly more frequent in pioglitazone responders than in nonresponders. The distribution of PGC-1 genotypes and alleles was not significantly different between responders and nonresponders. The decrease in fasting glucose (50.4 +/- 52.2 vs 43.3 +/- 51.7 mg/dL, P < .001) and hemoglobin A(1c) (0.57% +/- 1.44% vs 0.35% +/- 1.10%, P = .004) levels was significantly greater in subjects with the Ala12 carriers (Pro12Ala and Ala12Ala) than in those without the allele (Pro12Pro). Baseline fasting glucose and triglyceride levels were related to the response of pioglitazone. Only the PPAR-gamma Pro12Ala polymorphism was found to be associated with the response of pioglitazone by multiple logistic regression analysis. The PPAR-gamma Pro12Ala gene polymorphism is associated with the response to pioglitazone in Chinese patients with type 2 diabetes mellitus. These findings may be helpful for targeted treatment of diabetes by identifying patients who are likely to respond to pioglitazone.
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