title: The xylosyltransferase I gene polymorphism c.343G>T (p.A125S) is a risk factor for diabetic nephropathy in type 1 diabetes.
abstract: OBJECTIVE
  Xylosyltransferase I (XT-I) is the chain-initiating enzyme in the biosynthesis of proteoglycans in basement membranes. It catalyzes the transfer of xylose to selected serine residues in the core protein. The XYLT-II gene codes for a protein highly homologous to XT-I. Proteoglycans are important components of basement membranes and are responsible for their permeability properties. Type 1 diabetic patients have an altered proteoglycan metabolism, which results in microvascular complications. Thus, genetic variations in the xylosyltransferase genes might be implicated in the initiation and progression of these complications.
  
  
  METHODS
  Genotyping of four genetic variations in the genes XYLT-I and XYLT-II was performed in 912 type 1 diabetic patients (453 with and 459 without diabetic nephropathy) using restriction fragment-length polymorphism.
  
  
  RESULTS
  The distribution of the c.343G>T polymorphism in XYLT-I is significantly different between patients with and without diabetic nephropathy (P = 0.03). T-alleles were more frequent in patients with diabetic nephropathy (odds ratio 2.47 [95% CI 1.04-5.83]). The allelic frequencies of the other investigated XYLT-I and XYLT-II variations (XYLT-I: c.1989T>C in exon 9; XYLT-II: IVS6-9T>C and IVS6-14_IVS6-13insG in intron 5; and c.2402C>G: p.T801R in exon 11) were not different between patients with and without diabetic nephropathy.
  
  
  CONCLUSIONS
  The XYLT-I c.343G>T polymorphism contributes to the genetic susceptibility to development of diabetic nephropathy in type 1 diabetic patients.
authors.affiliation: Institut für Laboratoriums und Transfusionsmedizin, Herz und Diabeteszentrum Nordrhein-Westfalen, 32545 Bad Oeynhausen, Germany.
authors.forename: Sylvia
authors.initials: S
authors.lastname: Schön
authors.forename: Christian
authors.initials: C
authors.lastname: Prante
authors.forename: Claudia
authors.initials: C
authors.lastname: Bahr
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; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D003928:Diabetic Nephropathies / Q000209:etiology* / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010430:Pentosyltransferases / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D000097608:UDP Xylose-Protein Xylosyltransferase
chemical_list: D010430:Pentosyltransferases; D000097608:UDP Xylose-Protein Xylosyltransferase