title: Mutations and intronic variants in the HNF-1 beta gene in a group of German and Czech Caucasians with type 2 diabetes mellitus and progressive diabetic nephropathy.
abstract: Mutations in the hepatocyte nuclear factor - 1 beta (HNF-1 beta) gene cause maturity onset diabetes of the young type 5 (MODY 5). A clinical feature of the resulting phenotype besides impaired glucose tolerance is a variety of renal abnormalities, ranging from renal cysts to end-stage renal failure. Using a candidate gene approach we investigated the prevalence of mutations in the HNF-1 beta gene in a group of 63 patients from two different European populations (33 Germans, 30 Czechs) with type 2 diabetes mellitus and diabetic nephropathy diagnosed by increased albuminuria (39 patients) or end-stage renal failure (24 patients). No mutations were found in any of the 9 exons or in a minimal promoter region. Three intronic variants (single nucleotide polymorphisms - SNPs) were detected. The frequencies of these variants showed no difference between the two studied populations and were comparable to data reported from healthy subjects. No association between SNPs or formed haplotypes and any clinical parameters (like age of disease onset, BMI and severity of renal failure) was found. The results confirm that the genetic variations in the HNF-1 beta gene would be a very uncommon cause of progressive nephropathy in patients with type 2 diabetes mellitus.
authors.affiliation: Department of Internal Medicine III, University Clinic Carl Gustav Carus of the Technical University Dresden, Germany. selisko@rcs.urz.tu-dresden.de
authors.forename: T
authors.initials: T
authors.lastname: Selisko
authors.forename: J
authors.initials: J
authors.lastname: Vcelák
authors.forename: B
authors.initials: B
authors.lastname: Bendlová
authors.forename: J
authors.initials: J
authors.lastname: Graessler
authors.forename: P E H
authors.initials: PE
authors.lastname: Schwarz
authors.forename: J
authors.initials: J
authors.lastname: Schulze
mesh_terms: D017668:Age of Onset; D000419:Albuminuria; D015992:Body Mass Index; D018153:Czech Republic; D004268:DNA-Binding Proteins / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D003928:Diabetic Nephropathies / Q000235:genetics; D003929:Diabetic Neuropathies / Q000235:genetics*; D014644:Genetic Variation; D005858:Germany; D051539:Hepatocyte Nuclear Factor 1-beta; D006801:Humans; D007438:Introns; D007676:Kidney Failure, Chronic / Q000235:genetics; D008875:Middle Aged; D009154:Mutation; D014157:Transcription Factors / Q000235:genetics*; D044465:White People / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; C496495:HNF1B protein, human; D014157:Transcription Factors; D051539:Hepatocyte Nuclear Factor 1-beta