Song Jin-Fang, Wang Tao, Zhu Jing, Zhou Xue-Yan, Lu Qian, Guo Hao, Zhang Fan, Wang Yan, Li Wei, Wang Dan-Dan, Cui Ya-Wen, Lv Dong-Mei, Yin Xiao-Xing
Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical College, Xuzhou, China; Department of Pharmacy, Wuxi Third People's Hospital, Wuxi, China.
Clin Exp Pharmacol Physiol. 2015 Jan;42(1):27-32. doi: 10.1111/1440-1681.12314.
Repaglinide is a short-acting insulin secretagogue, which often results in considerable interindividual variability in therapeutic efficacy when widely used in a clinical setting. Among various reasons under discussion is genetic polymorphism, especially the genes related to insulin secretion and resistance. Recent studies have described the importance of PPARD in regulating the secretion and resistance of insulin. However, little is known about the impacts of PPARD genetic polymorphism on the efficacy of repaglinide. Therefore, the current study was designed to investigate the associations of PPARD rs2016520 polymorphism with type 2 diabetes mellitus (T2DM) susceptibility and repaglinide therapeutic efficacy in Chinese Han T2DM patients. A total of 338 T2DM patients and 200 healthy subjects were genotyped for PPARD rs2016520 polymorphism by polymerase chain reaction-restriction fragment length polymorphism assay. A total of 84 patients with the same genotypes of CYP2C8*3 139Arg and OATP1B1 521TT were randomized to orally take repaglinide for 8 weeks. Then the pharmacodynamic parameters of repaglinide and biochemical indicators were determined before and after repaglinide treatment. No significant difference was found in either allelic frequency (P = 0.298) or genotype distribution (P = 0.151) of PPARD rs2016520 between T2DM patients and healthy subjects. However, T2DM patients carrying genotype TC showed a significantly lower increase in postprandial serum insulin (mU/L) than those with wild-type TT (P < 0.05). These findings suggest that PPARD rs2016520 polymorphism might influence the therapeutic effect of repaglinide rather than T2DM susceptibility in Chinese Han T2DM patients.
瑞格列奈是一种短效胰岛素促泌剂，在临床广泛应用时，其治疗效果往往存在较大的个体差异。正在探讨的各种原因中包括基因多态性，尤其是与胰岛素分泌和抵抗相关的基因。最近的研究描述了过氧化物酶体增殖物激活受体δ（PPARD）在调节胰岛素分泌和抵抗中的重要性。然而，关于PPARD基因多态性对瑞格列奈疗效的影响知之甚少。因此，本研究旨在探讨中国汉族2型糖尿病（T2DM）患者中PPARD rs2016520多态性与T2DM易感性及瑞格列奈治疗效果的相关性。采用聚合酶链反应-限制性片段长度多态性分析对338例T2DM患者和200例健康受试者进行PPARD rs2016520多态性基因分型。将84例细胞色素P450 2C8（CYP2C8）*3 139Arg和有机阴离子转运多肽1B1（OATP1B1）521TT基因型相同的患者随机分组，口服瑞格列奈8周。然后在瑞格列奈治疗前后测定瑞格列奈的药效学参数和生化指标。T2DM患者与健康受试者之间PPARD rs2016520的等位基因频率（P = 0.298）或基因型分布（P = 0.151）均无显著差异。然而，携带基因型TC的T2DM患者餐后血清胰岛素（mU/L）的升高幅度显著低于野生型TT患者（P < 0.05）。这些发现表明，在中国汉族T2DM患者中，PPARD rs2016520多态性可能影响瑞格列奈的治疗效果，而不是T2DM易感性。
