Studies of the variability of the hepatocyte nuclear factor-1² (HNF-1² / TCF2) and the dimerization cofactor of HNF-1 (DcoH / PCBD) genes in relation to type 2 diabetes mellitus and ²-cell function

Mutations in the homeodomain-containing transcription factor hepatocyte nuclear factor-1² (HNF-1²) are known to cause a rare subtype of maturity-onset diabetes of the young (MODY5), which is associated with early-onset progressive non-diabetic renal dysfunction. To investigate whether mutations in H...

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Published in:Human mutation 2001-10, Vol.18 (4), p.356
Main Authors: Ek, Jakob, Grarup, Niels, Urhammer, Søren A, Gæde, Peter H, Drivsholm, Thomas, Borch-Johnsen, Knut, Hansen, Torben, Pedersen, Oluf
Format: Article
Language:English
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Summary:Mutations in the homeodomain-containing transcription factor hepatocyte nuclear factor-1² (HNF-1²) are known to cause a rare subtype of maturity-onset diabetes of the young (MODY5), which is associated with early-onset progressive non-diabetic renal dysfunction. To investigate whether mutations in HNF-1· are implicated in the pathogenesis of MODY or late-onset diabetes with and without nephropathy in Danish Caucasians we examined the HNF-1² (TCF2) and the dimerization cofactor of HNF-1 (DCoH, PCBD) genes for mutations in 11 MODY probands, 28 type 2 diabetic patients with nephropathy, and 46 type 2 diabetic patients with an impaired ²-cell function by combined single-strand conformation polymorphism (SSCP) and heteroduplex analysis. Analysis of the promoter and nine exons including intron-exon boundaries of the HNF-1² gene revealed one novel silent polymorphism and three previously reported intronic variants. The silent polymorphism (I91I) was found in one patient with late-onset type 2 diabetes. One of the intronic variant (IVS6+26T[arrow right]C) was examined further. Among 584 type 2 diabetic patients the allelic frequency was 13.1% (11.2-15.0%) compared to 11.6% (8.6-14.5%) in 229 glucose tolerant control subjects (NS). No difference in insulin secretion during an OGTT was seen between carriers of the different IVS6+26T[arrow right]C genotypes among the 229 middle-aged control subjects, nor among 302 glucose tolerant 60-year-old Danish Caucasians. Mutation analysis of the four exons comprising the DCoH gene revealed a previously described A[arrow right]G polymorphism located in the 3' untranslated region, which was not investigated further. In conclusion, mutations in HNF-1² and DCoH are not a major cause of MODY or late onset type 2 diabetes in Danish Caucasian subjects. Hum Mutat 18:356-357, 2001. © 2001 Wiley-Liss, Inc.
ISSN:1059-7794
1098-1004