Genetic variation of Neurogenin 3 is slightly associated with hyperproinsulinaemia and progression toward type 2 diabetes

Exp Clin Endocrinol Diabetes. 2008 Mar;116(3):178-83. doi: 10.1055/s-2007-992156. Epub 2007 Oct 12.

Abstract

Objective: Transcription factor Neurogenin 3 (NGN3) is considered as a candidate gene for the development of type 2 diabetes. The aim of the current study was to investigate the relevance of NGN3 variants for the clinical spectrum of diabetes development and disease progressions.

Research design and methods: A total of 552 subjects with increased risk of type 2 diabetes were investigated. They underwent a 75 g OGTT with measurements of plasma glucose, insulin and proinsulin at fasting and at 30, 60, 90 and 120 minutes after the glucose challenge, repeated after 3 years. The NGN3 SNPs, Gly167Arg and Ser199Phe were genotyped.

Result: Patients with type 2 diabetes carrying the variant genotype at SNP199 presented with significantly higher proinsulin levels. Proinsulin level was also associated with progression of diabetes mellitus. There was a discrete association of the Ser199Phe variant with evolution of the disease status.

Conclusion: A genetic variation in NGN3 gene may be among the genetic determinants involved in the pathogenesis of diabetes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Amino Acid Substitution
  • Basic Helix-Loop-Helix Transcription Factors / genetics*
  • Body Mass Index
  • Diabetes Mellitus, Type 2 / genetics*
  • Disease Progression
  • Genetic Variation*
  • Genotype
  • Germany
  • Humans
  • Hyperinsulinism / genetics*
  • Insulin / blood
  • Middle Aged
  • Nerve Tissue Proteins / genetics*
  • Polymorphism, Single Nucleotide
  • Proinsulin / blood*
  • Waist-Hip Ratio

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Insulin
  • NEUROG3 protein, human
  • Nerve Tissue Proteins
  • Proinsulin