title: Effects of NOS1AP rs12742393 polymorphism on repaglinide response in Chinese patients with type 2 diabetes mellitus.
abstract: OBJECTIVE
  To investigate the associations of NOS1AP rs12742393 polymorphism with the risk of type 2 diabetes mellitus (T2DM) and repaglinide therapeutic efficacy in Chinese patients with T2DM.
  
  
  METHODS
  Prospective case-control study.
  
  
  METHODS
  Academic medical center.
  
  
  METHODS
  A total of 300 patients with T2DM and 200 healthy volunteers were enrolled to identify NOS1AP rs12742393 genotypes using the polymerase chain reaction-restriction fragment length polymorphism assay. Eighty-four patients with various genotypes were randomly selected to receive oral repaglinide as a single-agent therapy (3 mg/day) for 8 weeks.
  
  
  RESULTS
  Anthropometric measurements and fasting plasma glucose (FPG), postprandial plasma glucose, hemoglobin A1c , fasting serum insulin (FINS), postprandial serum insulin, homeostasis model assessment for insulin resistance (HOMA-IR), triglyceride, total cholesterol, low-density lipoprotein-cholesterol, and high-density lipoprotein-cholesterol tests were obtained before and after repaglinide treatment. The risk C allelic frequency of NOS1AP rs12742393 was higher in patients with T2DM than in healthy volunteers (p<0.001). Patients with T2DM and genotypes AA and AC at NOS1AP rs12742393 had a significant reduction in FPG (mmol/l) compared with those with genotype CC (p<0.01). Patients with CC homozygotes and AC heterozygotes had a greater increase in FINS (mU/l) than those with wild-type AA (p<0.05). In addition, the carriers of genotype CC at NOS1AP rs12742393 had higher differential values of HOMA-IR compared with genotypes AC and AA carriers (p<0.001). The effects of repaglinide treatment on FPG (p<0.01), FINS (p<0.05) and HOMA-IR (p<0.001) were reduced in patients with T2DM carrying the NOS1AP rs12742393 risk C allele compared with the AA genotype carriers.
  
  
  CONCLUSIONS
  The NOS1AP rs12742393 polymorphism is associated with therapeutic efficacy of repaglinide in Chinese T2DM patients.
authors: Key Laboratory of New Drugs and Clinical Application, Xuzhou Medical College, Xuzhou, China; Department of Pharmacy, the Affiliated Hospital of Xuzhou Medical College, Xuzhou, China.
authors: Tao
authors: T
authors: Wang
authors: Yan
authors: Y
authors: Wang
authors: Dong-Mei
authors: DM
authors: Lv
authors: Jin-Fang
authors: JF
authors: Song
authors: Qian
authors: Q
authors: Lu
authors: Xing
authors: X
authors: Gao
authors: Fan
authors: F
authors: Zhang
authors: Hao
authors: H
authors: Guo
authors: Wei
authors: W
authors: Li
authors: Xiao-Xing
authors: XX
authors: Yin
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000328:Adult; D000483:Alleles; D044466:Asian People / Q000235:genetics; D001786:Blood Glucose / Q000187:drug effects; D002219:Carbamates / Q000627:therapeutic use*; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010880:Piperidines / Q000627:therapeutic use*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D011446:Prospective Studies
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D001786:Blood Glucose; D002219:Carbamates; D007004:Hypoglycemic Agents; C488081:NOS1AP protein, human; D010880:Piperidines; C072379:repaglinide
keywords: NOS1AP rs12742393; genetic polymorphism; repaglinide; type 2 diabetes mellitus