Anti-XYLT2 polyclonal antibody

Mucopolysaccharidoses ( MPS) are severe inherited metabolic disorders from the group of lysosomal storage diseases. They are caused by deficiency in the activity of enzymes involved in the degradation of glycosaminoglycans (GAGs) and resultant accumulation of these compounds in the cells of patients. Although enzyme replacement therapy has become available for some MPS types ( MPS I, MPS II and MPS VI), this treatment is not efficient when neurological symptoms occur, especially in MPS III ( Sanfilippo disease). Recent studies indicated that substrate reduction therapy (SRT) may be an effective option for the treatment of neurodegenerative lysosomal storage diseases, including MPS III. However, previous attempts to SRT for MPS III focused on the use of non-specific inhibitors of GAG synthesis. Thus, we aimed to use the small interfering RNA ( siRNA) procedure to control expression of particular genes, whose products are involved in GAG synthesis. In this report we show that, in MPS IIIA fibroblasts, we were able to reduce mRNA levels of four genes, XYLT1, XYLT2, GALTI and GALTII, whose products are involved in GAG synthesis. This decrease in levels of transcripts corresponded to a decrease in levels of proteins encoded by them. Moreover, efficiency of GAG production in these fibroblasts was considerably reduced after treatment of the cells with siRNA. These results indicate that efficient reduction of GAG synthesis may be achieved by the use of siRNA. European Journal of Human Genetics (2010) 18, 200-205; doi: 10.1038/ejhg.2009.144; published online 19 August 2009

BACKGROUND An accumulation of extracellular matrix molecules, such as proteoglycans, is observed in the vascular wall of hypertensive patients. Xylosyltransferases I and II (XT-I and XT-II), the chain-initiating enzymes in the biosynthesis of proteoglycans, catalyze the transfer of D-xylose from UDP-D-xylose to specific serine residues of the core protein. Because associations between XYLT polymorphisms and an altered blood pressure have been observed, genetic variations in the XYLT genes might predispose to essential hypertension. The localization of the XYLT2 gene on chromosome 17q increases its attractiveness as this region has been reported to be a potential candidate locus for essential hypertension. METHODS Genotyping of four polymorphisms in the genes XYLT1 and XYLT2 was performed in 150 unrelated essential hypertension patients and 150 age- and sex-matched normotensive controls using restriction fragment length polymorphism analysis. RESULTS The allele and genotype frequencies of the XYLT variants investigated did not show any significant differences between patients and controls, among allele-carriers and nonallele-carriers and among recessive and nonrecessive allele-carriers comparing patients and controls. Systolic and diastolic blood pressures did not differ significantly between the genotypes concerning all XYLT variants analyzed. Two XYLT2 variants deviated from Hardy-Weinberg equilibrium (HWE) in the hypertensive group. CONCLUSIONS No statistically significant association was found between four XYLT variants and hypertension or blood pressure, suggesting that they do not play a significant role in the development of essential hypertension. The deviation from HWE of two XYLT2 variants might be due to gene-phenotype associations which remain to be explored, as well as the possibility of gene-gene interactions.