title: PPARD rs2016520 polymorphism affects repaglinide response in Chinese Han patients with type 2 diabetes mellitus.
abstract: 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.
authors.affiliation: 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.
authors.forename: Jin-Fang
authors.initials: JF
authors.lastname: Song
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.forename: Jing
authors.initials: J
authors.lastname: Zhu
authors.forename: Xue-Yan
authors.initials: XY
authors.lastname: Zhou
authors.forename: Qian
authors.initials: Q
authors.lastname: Lu
authors.forename: Hao
authors.initials: H
authors.lastname: Guo
authors.forename: Fan
authors.initials: F
authors.lastname: Zhang
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Dan-Dan
authors.initials: DD
authors.lastname: Wang
authors.forename: Ya-Wen
authors.initials: YW
authors.lastname: Cui
authors.forename: Dong-Mei
authors.initials: DM
authors.lastname: Lv
authors.forename: Xiao-Xing
authors.initials: XX
authors.lastname: Yin
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics*; D002219:Carbamates / Q000494:pharmacology / Q000627:therapeutic use*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000235:genetics*; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D007328:Insulin / Q000097:blood; D008297:Male; D008875:Middle Aged; D047494:PPAR delta / Q000235:genetics*; D010880:Piperidines / Q000494:pharmacology / Q000627:therapeutic use*; D011110:Polymorphism, Genetic / Q000235:genetics; D019518:Postprandial Period / Q000187:drug effects / Q000502:physiology; D016896:Treatment Outcome
chemical_list: D002219:Carbamates; D007004:Hypoglycemic Agents; D007328:Insulin; D047494:PPAR delta; D010880:Piperidines; C072379:repaglinide
keywords: PPARD rs2016520; polymorphism; repaglinide; response; type 2 diabetes