Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “MODY”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 253 records · Page 14Linked to original sources
PubMed1995

Animal model for maturity-onset diabetes of the young generated by disruption of the mouse glucokinase gene.

Glucokinase catalyzes a rate-limiting step in glucose metabolism in hepatocytes and pancreatic beta cells and is considered the "glucose sensor" for regulation of insulin secretion. Patients with maturity-onset diabetes of the young (MODY) have heterozygous point mutations in the glucokinase gene that result in reduced enzymatic activity and decreased insulin secretion. However, it remains unclear whether abnormal liver glucose metabolism contributes to the MODY disease. Here we show that disruption of the glucokinase gene results in a phenotype similar to MODY in heterozygous mice. Reduced islet glucokinase activity causes mildly elevated fasting blood glucose levels. Hyperglycemic clamp studies reveal decreased glucose tolerance and abnormal liver glucose metabolism. These findings demonstrate a key role for glucokinase in glucose homeostasis and implicate both islets and liver in the MODY disease.

Animals↗
PubMed2001

A distant upstream promoter of the HNF-4alpha gene connects the transcription factors involved in maturity-onset diabetes of the young.

Maturity-onset diabetes of the young (MODY) is a monogenic, autosomal dominant subtype of early-onset diabetes mellitus due to defective insulin secretion by the pancreatic beta-cell in humans. Five different genes have been identified including those encoding the tissue-specific transcription factors expressed in pancreatic beta-cells, i.e. HNF-4alpha (MODY1), HNF-1alpha (MODY3), IPF-1 (also known as PDX-1, MODY4) and HNF-1beta (MODY5). Analyzing the transcription of the HNF-4alpha gene, we now identify an alternative promoter, P2, which is 46 kb 5' to the previously identified P1 promoter of the human gene. Based on RT-PCR this distant upstream P2 promoter represents the major transcription site in pancreatic beta-cells, but is also used in hepatic cells. Transfection assays with various deletions and mutants of the P2 promoter reveal functional binding sites for HNF-1alpha, HNF-1beta and IPF-1, the other transcription factors known to encode MODY genes. We demonstrate the significance of this alternative promoter in a large MODY family where a mutated IPF-1 binding site in the P2 promoter of the HNF-4alpha gene co-segregates with diabetes (LOD score 3.25). These data suggest a regulatory network of the four MODY transcription factors interconnected at the distant upstream P2 promoter of the HNF-4alpha gene.

Adult↗
PubMed2000

Naturally occurring mutations in the human HNF4alpha gene impair the function of the transcription factor to a varying degree.

The hepatocyte nuclear factor (HNF)4alpha, a member of the nuclear receptor superfamily, regulates genes that play a critical role in embryogenesis and metabolism. Recent studies have shown that mutations in the human HNF4alpha gene cause a rare form of type 2 diabetes, maturity onset diabetes of the young (MODY1). To investigate the properties of these naturally occurring HNF4alpha mutations we analysed five MODY1 mutations (R154X, R127W, V255M, Q268X and E276Q) and one other mutation (D69A), which we found in HepG2 hepatoma cells. Activation of reporter genes in transfection assays and DNA binding studies showed that the MODY1-associated mutations result in a variable reduction in function, whereas the D69A mutation showed an increased activity on some promoters. None of the MODY mutants acted in a dominant negative manner, thus excluding inactivation of the wild-type factor as a critical event in MODY development. A MODY3-associated mutation in the HNF1alpha gene, a well-known target gene of HNF4alpha, results in a dramatic loss of the HNF4 binding site in the promoter, indicating that mutations in the HNF4alpha gene might cause MODY through impaired HNF1alpha gene function. Based on these data we propose a two-hit model for MODY development.

Basic Helix-Loop-Helix Leucine Zipper Transcriptio↗
PubMed2005

Mechanisms of mutual functional interactions between HNF-4alpha and HNF-1alpha revealed by mutations that cause maturity onset diabetes of the young.

Hepatic nuclear factor (HNF)-4alpha and HNF-1alpha are key endodermal transcriptional regulators that physically and functionally interact. HNF-4alpha and HNF-1alpha cooperatively activate genes with binding sites for both factors, whereas suppressive interactions occur at regulatory sequences with a binding site for only one factor. The liver fatty acid binding protein gene (Fabp1) has binding sites for both factors, and chromatin precipitation assays were utilized to demonstrate that HNF-4alpha increased HNF-1alpha Fabp1 promoter occupancy during cooperative transcriptional activation. The HNF4 P2 promoter contains a HNF-1 but not HNF-4 binding site, and HNF-4alpha suppressed HNF-1alpha HNF4 P2 activation and decreased promoter HNF-1alpha occupancy. The apolipoprotein C III (APOC3) promoter contains a HNF-4 but not HNF-1 binding site, and HNF-1alpha suppressed HNF-4alpha APOC3 activation and decreased HNF-4alpha promoter occupancy. Maturity onset diabetes of the young (MODY) as well as defects in hepatic lipid metabolism result from mutations in either HNF-4alpha or HNF-1alpha. We found that MODY missense mutant R127W HNF-4alpha retained wild-type individual Fabp1 activation and bound to HNF-1alpha better than wild-type HNF-4alpha, yet did not cooperate with HNF-1alpha or increase HNF-1alpha Fabp1 promoter occupancy. The R127W mutant was also defective in both suppressing HNF-1alpha activation of HNF4 P2 and decreasing HNF-1alpha promoter occupancy. The HNF-1alpha R131Q MODY mutant also retained wild-type Fabp1 activation and bound to HNF-4alpha as well as the wild type but was defective in both suppressing HNF-4alpha APOC3 activation and decreasing HNF-4alpha promoter occupancy. These results suggest HNF-1alpha-HNF-4alpha functional interactions are accomplished by regulating factor promoter occupancy and that defective factor-factor interactions may contribute to the MODY phenotype.

Caco-2 Cells↗
PubMed1999

Defective mutations in the insulin promoter factor-1 (IPF-1) gene in late-onset type 2 diabetes mellitus.

Type 2 diabetes mellitus is a common disabling disease with onset in middle-aged individuals, caused by an imbalance between insulin production and action. Genetic studies point to major genetic components, but, with the exception of maturity-onset diabetes of the young (MODY), specific diabetes susceptibility genes remain to be identified. Recent studies showed that a dominant negative mutation in the insulin promoter factor-1 (IPF-1), a pancreatic beta-cell specific transcription factor, causes pancreatic agenesis and MODY. Thus, we investigated 192 French, non-MODY type 2 diabetic families for mutations in IPF-1. We identified 3 novel IPF-1 mutations, including 2 substitutions (Q59L and D76N) and an in-frame proline insertion (InsCCG243). Functional transactivation assays of these IPF-1 mutant isoforms in a beta-pancreatic tumor cell line transfected with a transcriptional reporter and IPF-1 expression plasmids demonstrate a significant inhibition of basal insulin promoter activity (stronger with the InsCCG243 mutant). We find that the InsCCG243 mutation is linked, in 2 families, to an autosomal dominant-like late-onset form of type 2 diabetes, in which insulin secretion becomes progressively impaired. The lower penetrance D76N and Q59L mutations were more prevalent and were associated with a relative risk of 12.6 for diabetes and with decreased glucose-stimulated insulin-secretion in nondiabetic subjects. We propose that IPF-1 mutations can cause MODY or apparently monogenic late-onset diabetes and that they represent a significant risk factor for type 2 diabetes in humans.

Blood Glucose↗
PubMedDate not supplied

Maturity-onset diabetes of the young: recent findings indicate insulin resistance/obesity are not factors.

Maturity-onset diabetes of the young (MODY) is a relatively rare subtype of type 2 diabetes characterized by an early age of onset and autosomal dominant inheritance. Unlike type 2 diabetes, which is often associated with insulin resistance, MODY is caused by a primary defect in pancreatic beta-cell function resulting in a decrease in insulin secretion. Obesity is not a feature of MODY. However, environmental stressors that increase the demand for insulin, such as illness or puberty, may unmask the genetically limited insulin secretory reserve of the undiagnosed MODY patient. Euglycemia is the primary goal of therapy, and diet is the cornerstone of glycemic control. Sulfonylureas and/or exogenous insulin may also be required depending on the degree of dysfunction of the beta cells.

Adult↗
PubMed1992

Identification of genetic markers flanking the locus for maturity-onset diabetes of the young on human chromosome 20.

A systematic search for genetic linkage with maturity-onset diabetes of the young (MODY) as expressed in the R.-W. pedigree has been carried out. Evidence for linkage was found with restriction-fragment-length polymorphism loci that map to human chromosome 20. Two-point linkage analysis with CRI-L1214 (D20S16) and MODY gave a log of the odds (lod) score of 4.16 at theta = 0.08. Multipoint linkage analysis with nine restriction-fragment-length polymorphism loci resulted in a lod score of 4.81 with the MODY locus in an approximately 20-cM region bounded by D20S16 and D20S14-D20S18. Examination of the pattern of MODY segregation suggests that additional factors, possibly genetic could be involved in the age of onset of the disease.

Adult↗
PubMed1995

Linkage analyses of the MODY3 locus on chromosome 12q with late-onset NIDDM.

Non-insulin-dependent diabetes mellitus (NIDDM) is a clinically and genetically heterogeneous disorder. Maturity-onset diabetes of the young (MODY), an autosomal dominant form of NIDDM, has been used as a model for genetic studies of NIDDM. We recently reported linkage between markers on chromosome 12q and diabetes in 25% of our French MODY families. To evaluate if this gene is also implicated in late-onset NIDDM, we performed linkage studies between two markers of the MODY region and diabetes in 172 families with late-onset NIDDM. Both parametric and nonparametric methods were used in a total of 600 affected sib-pairs. Linkage was rejected in this population by all methods, implying that the MODY gene on chromosome 12q is not a major gene for late-onset NIDDM in this population. However, we cannot exclude a modifying role in a polygenic disorder or an important role in some families.

Adult↗
PubMed1997

Mutations in the hepatocyte nuclear factor-1alpha gene are a common cause of maturity-onset diabetes of the young in the U.K.

Mutations in the hepatocyte nuclear factor-1alpha (HNF1alpha) gene have recently been shown to cause maturity-onset diabetes of the young (MODY). We have examined 15 U.K. MODY families for mutations in the coding region of the HNF-1alpha gene. Eight different mutations, three frameshift (P291fsinsC, P379fsdelCT, and A443fsdelCA) and five missense mutations (P129T, R131W, R159W, P519L, and T620I), were identified in eleven families (73%). The previously reported mutation P291fsinsC was found in four pedigrees. A screen of a further 32 probands with early onset (<40 years of age) NIDDM showed the mutation in two additional families. This common mutation was present on at least three different haplotypes, suggesting that its high frequency is due to recurrent mutation rather than a founder effect. We have demonstrated that mutations in the HNF-1alpha gene are a common cause of MODY in U.K. families and result in early onset NIDDM with a progressive clinical course. Mutation-based genetic counseling can now be considered for the majority of patients with MODY.

Adolescent↗
PubMed1997

Novel MODY3 mutations in the hepatocyte nuclear factor-1alpha gene: evidence for a hyperexcitability of pancreatic beta-cells to intravenous secretagogues in a glucose-tolerant carrier of a P447L mutation.

One form of maturity-onset diabetes of the young (MODY3) results from mutations in the hepatocyte nuclear factor (HNF)-1alpha gene, located on chromosome 12q24.2. The primary objective of the present study was to search for genetic variation in the HNF-1alpha gene in nine nonrelated Danish Caucasian subjects with MODY. Direct sequencing of the coding region and intron-exon boundaries of the HNF-1alpha gene revealed 2 novel and 1 previously reported missense mutations and 2 novel frameshift mutations in five of nine MODY subjects. These five mutations were found in neither 84 NIDDM patients nor 84 control subjects. One glucose-tolerant lean male with a P447L missense mutation, which in his relatives caused MODY, underwent an oral glucose tolerance test (OGTT), a tolbutamide modified frequently sampled intravenous glucose tolerance test, and a glucagon test to examine for a possible early beta-cell abnormality. He had a low insulin secretion rate during an OGTT, but a twofold increase in pancreatic beta-cell response after intravenous glucose and a 2.5- to 4-fold increase in beta-cell response after either intravenous tolbutamide or intravenous glucagon loads. In conclusion, 1) mutations in the HNF-1alpha gene are common in Danish Caucasian MODY patients, and 2) early stages in the pathogenesis of MODY3 caused by the P447L mutation may be characterized by a hyperexcitability of beta-cells to intravenous secretagogues.

Adolescent↗
PubMed1996

Diabetes complications in NIDDM kindreds linked to the MODY3 locus on chromosome 12q.

OBJECTIVE: To assess the prevalence of diabetes complications and the severity of diabetes in kindreds with NIDDM linked to the MODY3 locus (chromosome 12q) and to compare these parameters with data obtained in glucokinase (GCK)-deficient and other-MODY (unlinked to any of the three known loci) families, as well as with data from families with a late age of onset of NIDDM. RESEARCH DESIGN AND METHODS: Clinical and biological data were obtained from 667 affected members of 7 MODY3, 25 GCK-deficient, 6 other-MODY, and 81 NIDDM families. Severity of diabetes (glucose tolerance status and insulin secretion) was assessed by an oral glucose tolerance test. Neurological examination and eye fundus examination were performed in 349 and 251 subjects, respectively, and proteinuria was tested with strips in 282 family members. RESULTS: A higher prevalence of proliferative retinopathy was observed in MODY3 (21%) and NIDDM subjects (23%) than in GCK-deficient (3%) and other-MODY subjects (8%; P = 0.004). Proteinuria was detected in 19, 7, 5, and 0% (P = 0.07) of subjects, respectively. Prevalence of neuropathy was higher in NIDDM (17%; P = 0.005) than in MODY3 (4%), GCK-deficient (5%) and other-MODY (0%) subjects. MODY3 and NIDDM subjects had significantly higher fasting glucose levels than subjects in the other groups. Glucose levels after 2 h were significantly higher, and the ratios of insulin to glucose levels were significantly lower in MODY3 subjects than in the other three groups. CONCLUSIONS: The MODY3 subtype of NIDDM is characterized by a severe insulin secretory defect and by major hyperglycemia that progresses rapidly to overt diabetes. Microvascular complications of diabetes were frequently observed in the MODY3 subjects and the subjects with a late age of onset of NIDDM in this cohort. Both the duration and the severity of diabetes were independently associated with these complications.

Adolescent↗
PubMed1998

Liver and kidney function in Japanese patients with maturity-onset diabetes of the young.

OBJECTIVE: Heterozygous mutations in the transcription factors hepatocyte nuclear factor (HNF)-1 alpha, HNF-1 beta, and HNF-4 alpha are associated with maturity-onset diabetes of the young (MODY) and are believed to cause this form of diabetes by impairing pancreatic beta-cell function. The HNFs also play a central role in the tissue-specific regulation of gene expression in liver and kidney, suggesting that patients with MODY due to a mutation in HNF-1 alpha, HNF-1 beta, or HNF-4 alpha may exhibit abnormal liver or kidney function. Here, we have examined liver and kidney function in a series of Japanese patients with HNF-4 alpha/MODY1, HNF-1 alpha/MODY3, and HNF-1 beta/MODY5 diabetes. RESEARCH DESIGN AND METHODS: Clinical and biochemical data were obtained from Japanese subjects with HNF-1 alpha, HNF-1 beta, and HNF-4 alpha diabetes. The clinical data included information on BMI, age at diagnosis, current treatment, and the presence and nature of any complications. The biochemical studies examined liver and kidney function and included measures of alanine and aspartate aminotransferase, gamma-glutamyl transpeptidase, blood urea nitrogen, creatinine, uric acid, total and HDL cholesterol, triglycerides, and 17 serum proteins. RESULTS: The present age and duration of diabetes were similar in patients with HNF-1 alpha, HNF-1 beta, or HNF-4 alpha diabetes, as was the age at diagnosis of diabetes in the youngest generation. All subjects were lean. Of the subjects with HNF-1 alpha and HNF-4 alpha diabetes, 50% were treated with insulin, as were all three subjects with HNF-1 beta diabetes. Retinopathy was present in patients with each form of diabetes. None of the subjects with HNF-4 alpha diabetes had evidence of nephropathy, whereas 36% of the patients with HNF-1 alpha diabetes and 100% of those with HNF-1 beta diabetes showed diminished kidney function. The three subjects with HNF-1 beta diabetes also had abnormally high serum creatinine, uric acid, and blood urea nitrogen levels, which are consistent with impaired kidney function, and one of seven subjects with HNF-1 alpha diabetes had a mild elevation in creatinine and blood urea nitrogen levels. These values were within the normal range in the three patients with HNF-4 alpha diabetes. Although the HNFs play a role in regulating the expression of the genes for most, if not all, serum proteins, there was no decrease in the levels of any of the 17 serum proteins examined, and most were within or slightly above the normal range. Lipoprotein(a) [Lp(a)] levels were elevated in the three patients with HNF-4 alpha diabetes and in one patient with HNF-1 beta diabetes, and in a second patient with HNF-1 beta diabetes, Lp(a) was at the upper limit of normal. CONCLUSIONS: The results indicate that as in white patients, MODY resulting from mutations in the HNF-1 alpha, HNF-1 beta, and HNF-4 alpha genes in Japanese patients may be a severe disease similar to classic type 2 diabetes. In addition, they suggest that patients with HNF-1 beta diabetes may be characterized by diminished kidney function and perhaps abnormal liver function. Further studies are needed to determine whether tests of liver and kidney function will be useful in the diagnosis and subclassification of MODY.

Adolescent↗
PubMed1997

Maturity-onset diabetes of the young due to a mutation in the hepatocyte nuclear factor-4 alpha binding site in the promoter of the hepatocyte nuclear factor-1 alpha gene.

Recent studies have shown that mutations in the transcription factor hepatocyte nuclear factor (HNF)-1 alpha are the cause of one form of maturity-onset diabetes of the young (MODY3). These studies have identified mutations in the mRNA and protein coding regions of this gene that result in the synthesis of an abnormal mRNA or protein. Here, we report an Italian family in which an A-->C substitution at nucleotide-58 of the promoter region of the HNF-1 alpha gene cosegregates with MODY. This mutation is located in a highly conserved region of the promoter and disrupts the binding site for the transcription factor HNF-4 alpha, mutations in the gene encoding HNF-4 alpha being another cause of MODY (MODY1). This result demonstrates that decreased levels of HNF-1 alpha per se can cause MODY. Moreover, it indicates that both the promoter and coding regions of the HNF-1 alpha gene should be screened for mutations in subjects thought to have MODY because of mutations in this gene.

Animals↗
PubMed2005

[Molecular diagnosis on indication of maturity onset diabetes of the young; results from 184 patients].

OBJECTIVE: To describe the results of mutation analysis of the genes involved in maturity onset diabetes of the young (MODY) types 1-3. DESIGN: Descriptive. METHOD: In the period July 2000-October 2003 the DNA from 184 possible MODY patients was analysed for the presence of mutations of the genes involved in MODY types 1, 2 and 3. The patients fulfilled at least one of the following criteria: diabetes mellitus had been diagnosed before the age of 25, or at least before the age of 40, there was a family history of diabetes mellitus at an early age, there were no characteristics to indicate diabetes mellitus type 1 or 2. RESULTS: In the blood of 65 patients (35%) a pathogenic gene mutation was found. A total of 45 patients had a mutation in the HNF-1alpha-gene (which is linked to MODY3), 11 in the glucokinase gene (MODY2) and 9 in the HNF-4alpha-gene (MODY1). Of all the HNF-1alpha-gene mutations, the insertion of a C in codon 291 was the most frequently seen (in 11 families). A mutation in exon 9 of the HNF-1alpha-gene was also shown in 9 apparently non-related families, which probably was a founder mutation. CONCLUSION: The MODY subtype was found in one third of the selected patients. This diagnosis may have implications in the clinical management of the patient.

Adult↗
PubMed1987

Insulin resistance in maturity onset diabetes of the young.

Insulin resistance was assessed by euglycaemic clamp studies in matched groups of MODY, classical NIDDM patients and non-diabetic control subjects. The MODY patients metabolised less glucose (4.8 +/- 0.3 mg/Kg/min) than the classical NIDDM patients (7.0 +/- 0.5 mg/Kg/min) at an insulin infusion rate of 1.0 mU/Kg/min (p less than 0.05). At an insulin infusion rate 10 mU/Kg/min the differences between the MODY and the classical NIDDM patients were not significant. At both infusion rates the two diabetic groups metabolised less glucose than the control subjects. The results indicate that despite their younger age, the patients with MODY are more insulin resistant than the patients with classical NIDDM.

Adult↗
PubMed1998

[Non-insulin dependent diabetes in children and adolescents].

Maturity-onset diabetes of the young (MODY) is a clinically and genetically heterogenous disorder characterized by autosomal dominant inheritance with onset usually before 25 years of age, and a primary defect in glucose-stimulated insulin secretion. Genetic analyses have shown that mutations in at least five different genes can cause MODY. These are the genes encoding the glycolytic enzyme glucokinase, three liver-enriched transcription factors, hepatocyte nuclear factor (HNF)-1 alpha, HNF-1 beta and HNF-4 alpha, and the gene encoding the transcription factor, insulin promoter factor-1 (IPF-1). Patients with MODY3 run a considerable risk of developing diabetic eye disease. MODY2, related to glucokinase deficiency, is a relatively benign disorder which does not usually require insulin. Experiences with the three other MODY forms have so far been restricted to very few families. We present the first Norwegian family with MODY2. Furthermore, a previously published Norwegian family is shown to be MODY3. Subjects who fulfil the criteria of MODY can, by genetic testing, gain information important for prognosis and perhaps also for therapy.

Adolescent↗
PubMed1998

Nuclear factors and type 2 diabetes.

Recent studies have shown that mutations in four transcription factors, hepatocyte nuclear factor-4 alpha (HNF-4 alpha), hepatocyte nuclear factor-1 alpha (HNF-1 alpha), hepatocyte nuclear factor-1 beta (HNF-1 beta), and insulin promoter factor-1 (IPF-1), are responsible for maturity onset diabetes of the young (MODY) which is characterised by an early age of onset and autosomal dominant inheritance. MODY is not an uncommon disorder and in fact could account for about 2 to 5% of all cases of type 2 diabetes. Moreover, mutations in HNF-1 beta, which functions as a homodimer or a heterodimer with HNF-1 alpha, have been identified in a few families with MODY and severe kidney disease. Mutations in the coding regions or in the promotors of these nuclear factors are responsible for severe insulin secretory defects and for major hyperglycaemia associated with microvascular complications. The role of transcription factors in the development of the more common late-onset type 2 diabetes is still under investigation. Some mutations in HNF-1 alpha were identified in subjects with atypical forms of insulin-dependent diabetes, and a mutation in HNF-4 alpha and several mutations in IPF-1 were found in type 2 diabetic families with typical late-onset NIDDM. Altogether, these data suggest that non-MODY monofactorial forms of late-onset NIDDM, due to islet transcription factor defects, exist.

Adult↗
PubMed2001

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.

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.

Adult↗