title: Polymorphisms of GLP-1 receptor gene and response to GLP-1 analogue in patients with poorly controlled type 2 diabetes.
abstract: OBJECTIVE
  The relationship between genetic polymorphisms of the glucagon-like peptide-1 (GLP-1) receptor (GLP1R) gene and unresponsiveness to GLP-1 analogue treatment in patients with poorly controlled type 2 diabetes mellitus (DM) is unclear.
  
  
  METHODS
  Thirty-six patients with poorly controlled type 2 DM were enrolled and they received six days of continuous subcutaneous insulin infusion for this study. After the normalization of blood glucose in the first 3 days, the patients then received a combination therapy with injections of the GLP-1 analogue, exenatide, for another 3 days. All 13 exons and intron-exon boundaries of the GLP1R gene were amplified to investigate the association.
  
  
  RESULTS
  The short tandem repeat at 8GA/7GA (rs5875654) had complete linkage disequilibrium (LD, with r2 = 1) with single nucleotide polymorphism (SNP) rs761386. Quantitative trait loci analysis of GLP1R gene variation with clinical response of GLP1 analogue showed the missense rs3765467 and rs761386 significantly associated with changes in the standard deviation of plasma glucose (SDPG(baseline) - SDPG(treatment with GLP-1 analogue)) (P = 0.041 and 0.019, resp.). The reported P values became insignificant after multiple testing adjustments.
  
  
  CONCLUSIONS
  The variable response to the GLP-1 analogue was not statistically correlated with polymorphisms of the GLP1R gene in patients with poorly controlled type 2 DM.
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan ; Graduate Institute of Clinical Medical Sciences, Chang Gung University, Taoyuan 333, Taiwan.
authors.forename: Chia-Hung
authors.initials: CH
authors.lastname: Lin
authors.affiliation: Department of Biotechnology, Ming Chuan University, Taoyuan 333, Taiwan ; Genomic Medicine Research Core Laboratory, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan.
authors.forename: Yun-Shien
authors.initials: YS
authors.lastname: Lee
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan.
authors.forename: Yu-Yao
authors.initials: YY
authors.lastname: Huang
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan.
authors.forename: Sheng-Hwu
authors.initials: SH
authors.lastname: Hsieh
authors.affiliation: Graduate Institute of Clinical Medical Sciences, Chang Gung University, Taoyuan 333, Taiwan.
authors.forename: Zih-Syuan
authors.initials: ZS
authors.lastname: Chen
authors.affiliation: Graduate Institute of Clinical Medical Sciences, Chang Gung University, Taoyuan 333, Taiwan.
authors.forename: Chi-Neu
authors.initials: CN
authors.lastname: Tsai
mesh_terms: D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D005838:Genotype; D052216:Glucagon-Like Peptide 1 / Q000235:genetics* / Q000378:metabolism; D000067757:Glucagon-Like Peptide-1 Receptor / Q000235:genetics; D005951:Glucose Tolerance Test; D006760:Hospitalization; D006801:Humans; D007003:Hypoglycemia / Q000235:genetics; D055104:Infusions, Subcutaneous; D007328:Insulin / Q000008:administration & dosage / Q000627:therapeutic use; D015810:Linkage Disequilibrium; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D020125:Mutation, Missense; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci; D017422:Sequence Analysis, DNA
chemical_list: D001786:Blood Glucose; D000067757:Glucagon-Like Peptide-1 Receptor; D007328:Insulin; D052216:Glucagon-Like Peptide 1