PubMed:10491763 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PubMed/sourceid/10491763","sourcedb":"PubMed","sourceid":"10491763","source_url":"http://www.ncbi.nlm.nih.gov/pubmed/10491763","text":"Hepatocyte nuclear factor-6: associations between genetic variability and type II diabetes and between genetic variability and estimates of insulin secretion.\nAIMS/HYPOTHESIS: The transcription factor hepatocyte nuclear factor (HNF)-6 is an upstream regulator of several genes involved in the pathogenesis of maturity-onset diabetes of the young. We therefore tested the hypothesis that variability in the HNF-6 gene is associated with subsets of Type II (non-insulin-dependent) diabetes mellitus and estimates of insulin secretion in glucose tolerant subjects.\nMETHODS: We cloned the coding region as well as the intron-exon boundaries of the HNF-6 gene. We then examined them on genomic DNA in six MODY probands without mutations in the MODY1, MODY3 and MODY4 genes and in 54 patients with late-onset Type II diabetes by combined single strand conformational polymorphism-heteroduplex analysis followed by direct sequencing of identified variants. An identified missense variant was examined in association studies and genotype-phenotype studies.\nRESULTS: We identified two silent and one missense (Pro75 Ala) variant. In an association study the allelic frequency of the Pro75Ala polymorphism was 3.2% (95% confidence interval, 1.9-4.5) in 330 patients with Type II diabetes mellitus compared with 4.2% (2.4-6.0) in 238 age-matched glucose tolerant control subjects. Moreover, in studies of 238 middle-aged glucose tolerant subjects, of 226 glucose tolerant offspring of Type II diabetic patients and of 367 young healthy subjects, the carriers of the polymorphism did not differ from non-carriers in glucose induced serum insulin or C-peptide responses.\nCONCLUSION/INTERPRETATION: Mutations in the coding region of the HNF-6 gene are not associated with Type II diabetes or with changes in insulin responses to glucose among the Caucasians 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