, Volume 44, Issue 1, pp 123-126

Polymorphisms in the neurogenin 3 gene (NEUROG) and their relation to altered insulin secretion and diabetes in the Danish Caucasian population


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, Gly167Arg and Ser199Phe, 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 (χ 2 > 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.¶Conclusion/interpretation. 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. [Diabetologia (2001) 44: 123–126]

Received: 19 May 2000 and in revised form 12 September 2000