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

J Ek; N Grarup; S A Urhammer; P H Gaede; T Drivsholm; K Borch-Johnsen; T Hansen; O Pedersen

doi:10.1002/humu.1201

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

J Ek, N Grarup, S A Urhammer, P H Gaede, T Drivsholm, K Borch-Johnsen, T Hansen, O Pedersen

6 Citationer (Scopus)

Abstract

Mutations in the homeodomain-containing transcription factor hepatocyte nuclear factor-1beta (HNF-1beta) 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-1beta (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 beta-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-1beta 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-->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-->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-->G polymorphism located in the 3' untranslated region, which was not investigated further. In conclusion, mutations in HNF-1beta and DCoH are not a major cause of MODY or late onset type 2 diabetes in Danish Caucasian subjects.

Originalsprog	Engelsk
Tidsskrift	Human Mutation
Vol/bind	18
Udgave nummer	4
Sider (fra-til)	356-7
Antal sider	2
ISSN	1059-7794
DOI	https://doi.org/10.1002/humu.1201
Status	Udgivet - 1 okt. 2001

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Citationsformater

Ek, J., Grarup, N., Urhammer, S. A., Gaede, P. H., Drivsholm, T., Borch-Johnsen, K., Hansen, T., & Pedersen, O. (2001). Studies of the variability of the hepatocyte nuclear factor-1beta (HNF-1beta / TCF2) and the dimerization cofactor of HNF-1 (DcoH / PCBD) genes in relation to type 2 diabetes mellitus and beta-cell function. Human Mutation, 18(4), 356-7. https://doi.org/10.1002/humu.1201

Studies of the variability of the hepatocyte nuclear factor-1beta (HNF-1beta / TCF2) and the dimerization cofactor of HNF-1 (DcoH / PCBD) genes in relation to type 2 diabetes mellitus and beta-cell function. / Ek, J; Grarup, N; Urhammer, S A et al.

I: Human Mutation, Bind 18, Nr. 4, 01.10.2001, s. 356-7.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

Ek, J, Grarup, N, Urhammer, SA, Gaede, PH, Drivsholm, T, Borch-Johnsen, K, Hansen, T & Pedersen, O 2001, 'Studies of the variability of the hepatocyte nuclear factor-1beta (HNF-1beta / TCF2) and the dimerization cofactor of HNF-1 (DcoH / PCBD) genes in relation to type 2 diabetes mellitus and beta-cell function', Human Mutation, bind 18, nr. 4, s. 356-7. https://doi.org/10.1002/humu.1201

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

abstract = "Mutations in the homeodomain-containing transcription factor hepatocyte nuclear factor-1beta (HNF-1beta) 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-1beta (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 beta-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-1beta 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-->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-->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-->G polymorphism located in the 3' untranslated region, which was not investigated further. In conclusion, mutations in HNF-1beta and DCoH are not a major cause of MODY or late onset type 2 diabetes in Danish Caucasian subjects.",

keywords = "Adult, Age of Onset, Aged, Blood Glucose, DNA Mutational Analysis, DNA-Binding Proteins, Diabetes Mellitus, Type 2, Diabetic Nephropathies, European Continental Ancestry Group, Exons, Female, Gene Frequency, Glucose Tolerance Test, Hepatocyte Nuclear Factor 1-beta, Humans, Hydro-Lyases, Insulin, Introns, Islets of Langerhans, Male, Middle Aged, Netherlands, Phenotype, Polymorphism, Single-Stranded Conformational, Promoter Regions, Genetic, Transcription Factors",

author = "J Ek and N Grarup and Urhammer, {S A} and Gaede, {P H} and T Drivsholm and K Borch-Johnsen and T Hansen and O Pedersen",

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T1 - Studies of the variability of the hepatocyte nuclear factor-1beta (HNF-1beta / TCF2) and the dimerization cofactor of HNF-1 (DcoH / PCBD) genes in relation to type 2 diabetes mellitus and beta-cell function

AU - Ek, J

AU - Grarup, N

AU - Urhammer, S A

AU - Gaede, P H

AU - Drivsholm, T

AU - Borch-Johnsen, K

AU - Hansen, T

AU - Pedersen, O

PY - 2001/10/1

Y1 - 2001/10/1

N2 - Mutations in the homeodomain-containing transcription factor hepatocyte nuclear factor-1beta (HNF-1beta) 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-1beta (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 beta-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-1beta 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-->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-->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-->G polymorphism located in the 3' untranslated region, which was not investigated further. In conclusion, mutations in HNF-1beta and DCoH are not a major cause of MODY or late onset type 2 diabetes in Danish Caucasian subjects.

AB - Mutations in the homeodomain-containing transcription factor hepatocyte nuclear factor-1beta (HNF-1beta) 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-1beta (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 beta-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-1beta 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-->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-->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-->G polymorphism located in the 3' untranslated region, which was not investigated further. In conclusion, mutations in HNF-1beta and DCoH are not a major cause of MODY or late onset type 2 diabetes in Danish Caucasian subjects.

KW - Adult

KW - Age of Onset

KW - Aged

KW - Blood Glucose

KW - DNA Mutational Analysis

KW - DNA-Binding Proteins

KW - Diabetes Mellitus, Type 2

KW - Diabetic Nephropathies

KW - European Continental Ancestry Group

KW - Exons

KW - Female

KW - Gene Frequency

KW - Glucose Tolerance Test

KW - Hepatocyte Nuclear Factor 1-beta

KW - Humans

KW - Hydro-Lyases

KW - Insulin

KW - Introns

KW - Islets of Langerhans

KW - Male

KW - Middle Aged

KW - Netherlands

KW - Phenotype

KW - Polymorphism, Single-Stranded Conformational

KW - Promoter Regions, Genetic

KW - Transcription Factors

U2 - 10.1002/humu.1201

DO - 10.1002/humu.1201

M3 - Journal article

C2 - 11668623

SN - 1059-7794

VL - 18

SP - 356

EP - 357

JO - Human Mutation

JF - Human Mutation

IS - 4

ER -