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.