title: Novel sequence variants in the human xylosyltransferase I gene and their role in diabetic nephropathy.
abstract: OBJECTIVE
  Decreased content of heparan sulphate proteoglycans (HSPGs) is a characteristic of the glomerular basement membrane (GBM) in diabetes and contributes to the development of diabetic nephropathy (DN). Xylosyltransferase I (XT-I) is the chain-initiating enzyme involved in the biosynthesis of HSPGs. This study investigated a possible association between XYLT-I sequence variants and susceptibility to DN.
  
  
  METHODS
  Screening of all XYLT-I exons was performed in 74 caucasians with Type 1 diabetes (48 with and 26 without DN) and in 13 non-diabetic control subjects using denaturing high-performance liquid chromatography.
  
  
  RESULTS
  Fifteen XYLT-I sequence variants were identified. Of these, six were previously unknown. There were significant differences in the allele frequencies of the three polymorphisms (c.343G-->T (p.A115S), IVS3+10C-->T, IVS3+30G-->C) in Type 1 diabetic patients and healthy controls.
  
  
  CONCLUSIONS
  The occurrence of DN is independent of the XYLT-I variants detected in our study. However, three XYLT-I polymorphisms may be linked to Type 1 diabetes. Since we have previously proposed that one of these polymorphisms was not associated with Type 1 diabetes (Schön S et al. Kidney Int 2005; 68: 1483-1490), larger-scale analysis is clearly necessary to pinpoint the significance of this mutation.
authors.affiliation: Institut für Laboratoriums- und Transfusionsmedizin, Herz- und Diabeteszentrum Nordrhein-Westfalen, Universitätsklinik der Ruhr-Universität Bochum, Bad Oeynhausen, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Bahr
authors.forename: S
authors.initials: S
authors.lastname: Schön
authors.forename: J
authors.initials: J
authors.lastname: Kuhn
authors.forename: P H
authors.initials: PH
authors.lastname: Groop
authors.forename: M
authors.initials: M
authors.lastname: Parkkonen
authors.forename: M
authors.initials: M
authors.lastname: Wessman
authors.forename: K
authors.initials: K
authors.lastname: Kleesiek
authors.forename: C
authors.initials: C
authors.lastname: Götting
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D003928:Diabetic Nephropathies / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D010430:Pentosyltransferases / Q000235:genetics*; D011110:Polymorphism, Genetic; D000097608:UDP Xylose-Protein Xylosyltransferase
chemical_list: D010430:Pentosyltransferases; D000097608:UDP Xylose-Protein Xylosyltransferase