title: Polymorphisms in the neurogenin 3 gene (NEUROG) and their relation to altered insulin secretion and diabetes in the Danish Caucasian population.
abstract: AIM/HYPOTHESIS. Neurogenin 3 (NEUROG3) is a member of the subfamily of basic-helix-loop-helix (bHLH) transcription factors involved in differentiation of the endocrine pancreas and therefore a possible candidate gene for maturity-onset diabetes of the young (MODY) and Type II (non-insulin-dependent) diabetes mellitus.
  
  
  METHODS
  Using Polymerase-chain-reaction single-stranded-conformation polymorphism, we examined the coding region including the 5'-untranslated and 3'- untranslated regions of the NEUROG3 in a group of 133 diabetic patients comprising 19 MODY patients, 19 patients with dominant Type I diabetes, and 31 early-onset and 64 late-onset Type II diabetic patients.
  
  
  RESULTS
  We found two missense mutations, Glyl67Arg and Serl99Phe, as well as two non-coding variants in the 5' UTR, a c --> t nucleotide variant at position -10 upstream of the start codon in one MODY patient and a 2 base pair (CA) deletion polymorphism at position -44/-45. Allele frequencies measured in 377 diabetic patients and in 217 glucose-tolerant control subjects were: Gly167Arg, 0.04 (95 % CI: 0.02-0.06) and 0.04 (0.02-0.06); Ser199Phe, 0.31 (0.26-0.36) and 0.30 (0.24-0.36); -44-45delCA, 0.33 (0.31-0.35) and 0.35 (0.32-0.38), respectively. Both Ser199Phe and the -44-45delCA were in linkage disequilibrium (chi2 > 60) but the Ser199Phe and the -44-45delCA polymorphism were not associated with consistent changes in fasting- or glucose-induced insulin secretion in 249 glucose-tolerant offspring (first-degree relatives) of Type II diabetic parents or in 217 unrelated middle-aged glucose tolerant subjects.
  
  
  CONCLUSIONS
  Genetic variability in NEUROG3 is not associated with dominant Type I diabetes, MODY, Type II diabetes or changes in insulin secretion in the Danish Caucasians examined subjects.
authors.affiliation: Steno Diabetes Center, Copenhagen, Denmark.
authors.forename: J N
authors.initials: JN
authors.lastname: Jensen
authors.forename: L
authors.initials: L
authors.lastname: Hansen
authors.forename: C T
authors.initials: CT
authors.lastname: Ekstrøm
authors.forename: F
authors.initials: F
authors.lastname: Pociot
authors.forename: J
authors.initials: J
authors.lastname: Nerup
authors.forename: T
authors.initials: T
authors.lastname: Hansen
authors.forename: O
authors.initials: O
authors.lastname: Pedersen
mesh_terms: D020413:3' Untranslated Regions; D020121:5' Untranslated Regions; D000328:Adult; D000483:Alleles; D020029:Base Pairing; D051792:Basic Helix-Loop-Helix Proteins; D003718:Denmark; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D005787:Gene Frequency; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D009419:Nerve Tissue Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D018807:Polymorphism, Single-Stranded Conformational
chemical_list: D020413:3' Untranslated Regions; D020121:5' Untranslated Regions; D051792:Basic Helix-Loop-Helix Proteins; D007328:Insulin; D009419:Nerve Tissue Proteins; C498695:NEUROG3 protein, human