title: NeuroD1 A45T and PAX4 R121W polymorphisms are associated with plasma glucose level of repaglinide monotherapy in Chinese patients with type 2 diabetes.
abstract: OBJECTIVE
  We aimed to determine whether NeuroD1/BETA2 and PAX4 polymorphisms were associated with the therapeutic efficacy of repaglinide in Chinese type 2 diabetes mellitus (T2DM) patients.
  
  
  METHODS
  Three hundred and sixty-eight T2DM patients and 132 healthy control subjects were genotyped by restriction fragment length polymorphism. Forty-three patients with various genotypes were randomly selected to undergo 8 weeks of repaglinide treatment (3 mg day(-1)). Fasting plasma glucose, postprandial plasma glucose, glycated haemoglobin, fasting and postprandial serum insulin (FINS, PINS), homeostasis model assessment for insulin resistance, serum triglyceride, total cholesterol, low-density lipoprotein-cholesterol and high-density lipoprotein-cholesterol were determined before and after repaglinide treatment.
  
  
  RESULTS
  The allelic frequency of NeuroD1/BETA2 T45 was higher in T2DM patients than in the control subjects [13.45 vs. 6.82%, P < 0.01, odds ratios = 2.342 (1.365, 4.019), P= 0.002]. Type 2 diabetes mellitus patients with the mutated allele of NeuroD1/BETA2 A45T polymorphism showed higher FINS (13.46 ± 12.57 vs. 10.04 ± 7.09 mU l(-1) , P < 0.05) (11.67, 14.83 vs. 8.38, 11.37) and PINS (52.11 ± 40.93 vs. 68.66 ± 43.87 mU l(-1), P < 0.05) (44.89, 58.35 vs. 55.35, 88.87) than individuals with the T allele. The PAX4 R121W R allele carriers had higher PINS (52.11 ± 40.93 vs. 68.66 ± 43.87 mU l(-1), P < 0.05) (44.89, 58.35 vs. 55.35, 88.87) than subjects with the W allele. After repaglinide treatment, patients with the T allele of NeuroD1/BETA2 A45T polymorphisms had attenuated efficacy on fasting plasma glucose (-2.79 ± 2.14 vs.-0.99 ± 1.80 mmol l(-1), P < 0.01) (-3.53, -1.84 vs.-1.99, -0.13) and postprandial plasma glucose (-6.71 ± 5.90 vs.-2.54 ± 3.39 mmol l(-1), P < 0.01) (-9.28, -4.62 vs.-4.34, -0.84). Patients with the RR genotype of PAX4 R121W showed better efficacy with respect to the level of postprandial plasma glucose than R/W genotypes (-6.53 ± 6.52 vs.-2.95 ± 1.17 mmol l(-1), P < 0.05) (-8.20, -4.89 vs.-3.92, -1.20).
  
  
  CONCLUSIONS
  The NeuroD1/BETA2 and PAX4 polymorphisms were substantially associated with plasma glucose level after repaglinide monotherapy.
authors.affiliation: Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha, Hunan, China.
authors.forename: Zhi-Cheng
authors.initials: ZC
authors.lastname: Gong
authors.forename: Qiong
authors.initials: Q
authors.lastname: Huang
authors.forename: Xing-Ping
authors.initials: XP
authors.lastname: Dai
authors.forename: Guang-Hua
authors.initials: GH
authors.lastname: Lei
authors.forename: Hong-Bin
authors.initials: HB
authors.lastname: Lu
authors.forename: Ji-Ye
authors.initials: JY
authors.lastname: Yin
authors.forename: Xiao-Jing
authors.initials: XJ
authors.lastname: Xu
authors.forename: Jian
authors.initials: J
authors.lastname: Qu
authors.forename: Qi
authors.initials: Q
authors.lastname: Pei
authors.forename: Min
authors.initials: M
authors.lastname: Dong
authors.forename: Bo-Ting
authors.initials: BT
authors.lastname: Zhou
authors.forename: Jie
authors.initials: J
authors.lastname: Shen
authors.forename: Gan
authors.initials: G
authors.lastname: Zhou
authors.forename: Hong-Hao
authors.initials: HH
authors.lastname: Zhou
authors.forename: Zhao-Qian
authors.initials: ZQ
authors.lastname: Liu
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D044466:Asian People; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics*; D001786:Blood Glucose / Q000187:drug effects; D002219:Carbamates / Q000494:pharmacology*; D016022:Case-Control Studies; D002681:China; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000235:genetics; D005260:Female; D005838:Genotype; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D051761:Paired Box Transcription Factors / Q000235:genetics*; D010880:Piperidines / Q000494:pharmacology*; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D001786:Blood Glucose; D002219:Carbamates; D018398:Homeodomain Proteins; D007004:Hypoglycemic Agents; D051761:Paired Box Transcription Factors; D010880:Piperidines; C093970:NEUROD1 protein, human; C491709:PAX4 protein, human; C072379:repaglinide