Division of Endocrinology and Metabolism, Department of Internal Medicine, Kaohsiung Medical University/Chung-Ho Memorial Hospital, Kaohsiung 807, Taiwan.
Metabolism. 2010 Aug;59(8):1139-44. doi: 10.1016/j.metabol.2009.10.030. Epub 2009 Dec 31.
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.
我们研究了过氧化物酶体增殖物激活受体-γ（PPAR-γ；Pro12Ala）和过氧化物酶体增殖物激活受体-γ共激活因子-1（PGC-1；Gly482Ser）基因的常见多态性对中国 2 型糖尿病患者对吡格列酮反应的影响。共有 250 例 2 型糖尿病患者在不改变先前药物治疗的情况下接受吡格列酮（30mg/d）治疗 24 周。所有患者均进行 PPAR-γ Pro12Ala 和 PGC-1 Gly482Ser 多态性基因分型。吡格列酮应答者的 Ala12Ala 和 Pro12Ala 基因型（26.0%比 13.5%，P=.025）和 Ala 等位基因（15.6%比 7.3%，P=.008）显著高于无应答者。应答者和无应答者之间 PGC-1 基因型和等位基因的分布无显著差异。空腹血糖（50.4+/-52.2 比 43.3+/-51.7mg/dL，P<.001）和糖化血红蛋白（HbA1c）（0.57%+/-1.44%比 0.35%+/-1.10%，P=.004）的下降在携带 Ala12 的受试者中（Pro12Ala 和 Ala12Ala）比不携带该等位基因的受试者（Pro12Pro）更为显著。基线空腹血糖和甘油三酯水平与吡格列酮的反应有关。只有 PPAR-γ Pro12Ala 多态性通过多元逻辑回归分析被发现与吡格列酮的反应相关。PPAR-γ Pro12Ala 基因多态性与中国 2 型糖尿病患者对吡格列酮的反应有关。这些发现可能有助于通过识别可能对吡格列酮有反应的患者来对糖尿病进行有针对性的治疗。
