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Elevated xylosyltransferase I activities in pseudoxanthoma elasticum (PXE) patients as a marker of stimulated proteoglycan biosynthesis

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Abstract

Pseudoxanthoma elasticum (PXE) is a hereditary disorder of the connective tissue characterized by extracellular matrix alterations with elastin fragmentation and excessive proteoglycan deposition. Xylosyltransferase I (XT-I, E.C. 2.4.2.26) is the initial enzyme in the biosynthesis of the glycosaminoglycan chains in proteoglycans and has been shown to be a marker of tissue remodeling processes. Here, we investigated for the first time serum XT-I activities in a large cohort of German PXE patients and their unaffected relatives. XT-I activities were measured in serum samples from 113 Caucasian patients with PXE and 103 unaffected first-degree family members. The occurrence of the frequent ABCC6 gene mutation c.3421C>T (R1141X) and the hypertension-associated genetic variants T174M and M235T in the angiotensinogen (AGT) gene were determined. Serum XT-I activities in male and female PXE patients were significantly increased compared to unaffected family members (male patients, mean value 0.96 mU/l, SD 0.37; male relatives, 0.78 mU/l, SD 0.29; female patients, 0.91 mU/l, SD 0.31; female relatives, 0.76 mU/l, SD 0.34; p<0.05). The mean XT-I activities in PXE patients with hypertension were 24% higher than in patients without increased blood pressure (p<0.05). The AGT T174M and M235T frequencies were not different in hypertensive PXE patients, normotensive PXE patients, family members or blood donors. Our data show that the altered proteoglycan biosynthesis in PXE patients is closely related to an increased XT-I activity in blood. Serum XT-I, the novel fibrosis marker, may be useful for the assessment of extracellular matrix alterations and disease activity in PXE.

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Abbreviations

AGT:

Angiotensinogen

PXE:

Pseudoxanthoma elasticum

XT-I:

Xylosyltransferase I

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Acknowledgements

We would like to thank Marlen Ewald and Anja Reuße-Kaup for their excellent technical assistance and Sarah Kirkby for her linguistic advice. We are very grateful to all the PXE patients and their relatives, whose cooperation made this study possible. Furthermore, we would like to thank Peter Hof, chairman of the Selbsthilfe für PXE Erkrankte Deutschlands e.V., and the members of the clinical out-patients unit for PXE at the Bethesda hospital in Freudenberg, Germany.

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Authors and Affiliations

  1. Institut für Laboratoriums-und Transfusionsmedizin, Herz-und Diabeteszentrum Nordrhein-Westfalen, Universitätsklinik der Ruhr-Universität Bochum, Georgstrasse 11, 32545, Bad Oeynhausen, Germany

    Christian Götting, Doris Hendig, Alexandra Adam, Sylvia Schön, Veronika Schulz, Joachim Kuhn & Knut Kleesiek

  2. Dermatologische Klinik, Krankenhaus Bethesda, Freudenberg, Germany

    Christiane Szliska

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  1. Christian Götting
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  2. Doris Hendig
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Correspondence to Christian Götting.

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Götting, C., Hendig, D., Adam, A. et al. Elevated xylosyltransferase I activities in pseudoxanthoma elasticum (PXE) patients as a marker of stimulated proteoglycan biosynthesis. J Mol Med 83, 984–992 (2005). https://doi.org/10.1007/s00109-005-0693-x

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  • DOI: https://doi.org/10.1007/s00109-005-0693-x

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