Description:
<jats:p>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.</jats:p>
<jats:p>RESEARCH DESIGN AND 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.</jats:p>
<jats:p>RESULTS—The distribution of the c.343G&gt;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&gt;C in exon 9; XYLT-II: IVS6–9T&gt;C and IVS6–14_IVS6–13insG in intron 5; and c.2402C&gt;G: p.T801R in exon 11) were not different between patients with and without diabetic nephropathy.</jats:p>
<jats:p>CONCLUSIONS—The XYLT-I c.343G&gt;T polymorphism contributes to the genetic susceptibility to development of diabetic nephropathy in type 1 diabetic patients.</jats:p>