title: Identification of a xylosyltransferase II gene haplotype marker for diabetic nephropathy in type 1 diabetes.
abstract: BACKGROUND
  Proteoglycans are major components of the glomerular basement membrane, being responsible for their permeability properties. Type 1 diabetic patients have an altered proteoglycan metabolism, which contributes to microvascular complications like diabetic nephropathy. Xylosyltransferase II (XT-II) is a chain-initiating enzyme in the biosynthesis of basement membrane proteoglycans and catalyzes the transfer of xylose to selected serine residues in the core protein. Thus, genetic variations in the XT-II coding gene XYLT2 might be implicated in the initiation and progression of late diabetic complications.
  
  
  METHODS
  Genotyping of 6 genetic variations in the XYLT2 gene and haplotype analysis was performed in 697 type 1 diabetic patients (358 with and 338 without diabetic nephropathy).
  
  
  RESULTS
  The haplotype analysis of 6 XYLT2 polymorphisms revealed one haplotype (GATTCG) to be significantly less frequent among type 1 patients with diabetic nephropathy (p=0.002, OR=0.13, 95% CI=0.03-0.59). The haplotype GATTCG consist of the XYLT2 variations c.166G>A, c.177A>G, c.342T>C, IVS6-9T>C, c.1569C>T and c.2402C>G. No genotype-phenotype interactions were revealed.
  
  
  CONCLUSIONS
  Our data show that a XYLT2 haplotype is associated with nephropathy in type 1 diabetic patients.
authors.affiliation: Institut für Laboratoriums- und Transfusionsmedizin, Herz- und Diabeteszentrum Nordrhein-Westfalen, Universitätsklinik der Ruhr-Universität Bochum, Bad Oeynhausen, Germany.
authors.forename: Doris
authors.initials: D
authors.lastname: Hendig
authors.forename: Lise
authors.initials: L
authors.lastname: Tarnow
authors.forename: Joachim
authors.initials: J
authors.lastname: Kuhn
authors.forename: Knut
authors.initials: K
authors.lastname: Kleesiek
authors.forename: Christian
authors.initials: C
authors.lastname: Götting
mesh_terms: D000328:Adult; D000483:Alleles; D015415:Biomarkers; D004247:DNA / Q000235:genetics; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D003928:Diabetic Nephropathies / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D005819:Genetic Markers; D014644:Genetic Variation; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D010430:Pentosyltransferases / Q000235:genetics*; D010641:Phenotype; D000097608:UDP Xylose-Protein Xylosyltransferase
chemical_list: D015415:Biomarkers; D004247:DNA; D005819:Genetic Markers; D010430:Pentosyltransferases; D000097608:UDP Xylose-Protein Xylosyltransferase