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

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