The xylosyltransferase Ι gene polymorphism c.343G>T (p.A115S) is associated with decreased serum glycosaminoglycan levels

The xylosyltransferases I and II (XT-I, XT-II, EC 2.4.2.26) are the chain-initiating enzymes in the biosynthesis of glycosaminoglycans (GAGs). This is the first investigation of changes in the serum GAG amount and composition in association with polymorphisms in XYLT1 and XYLT2. Genotyping of three genetic variations in the genes XYLT1 and XYLT2 was performed in 223 healthy blood donor samples. Serum samples were analyzed for their GAG Δ-disaccharide content by reversed-phase high-performance liquid chromatography (RP-HPLC). Furthermore serum XT activity was determined by a radiochemical assay. The single nucleotide polymorphism (SNP) c.343G>T in XYLT1 exon 1 correlated with a significantly decreased GAG content in the serum ( p < 0.01). For the other two investigated XYLT2 variations (c.166G>A in exon 2 and c.1253C>T in exon 6) no changes in the serum GAG amount were detected. No investigated SNPs were associated with changes to serum XT activities. The XYLT1 SNP c.343G>T is associated with a decreased GAG amount in the serum of healthy blood donors.