Polymorphisms in the xylosyltransferase genes cause higher serum XT-I activity in patients with pseudoxanthoma elasticum (PXE) and are involved in a severe disease course.
Abnormal phenotype of in vitro dermal fibroblasts from patients with Pseudoxanthoma elasticum (PXE).
[3] Nonstandard abbreviations: PXE, pseudoxanthoma elasticum; MRP, multidrug resistance-associated protein; ROS, reactive oxygen species.
Clinical characteristics of PXE patients and healthy blood donors.
A number of genes are likely to contribute to PXE susceptibility.
Although we identified polymorphisms and haplotype patterns in the SPP1 promoter that may play a significant role in the pathogenesis of PXE by altering gene expression, the mechanisms by which these variants predispose patients to PXE are unknown.
Although the size of the PXE patient cohort was small, the power of the present study was adequate to detect an association of SPP1 promoter polymorphisms and susceptibility to PXE reliably.
The currently available ELISA assays are suitable for determination of SPP1 concentrations only in plasma samples, which were not available for the PXE patients and controls in this study.
Analysis of the fetuin-A polymorphisms c.742C>T (p.T248M) and c.766C>G (p.T256S) in PXE patients, relatives, and healthy controls revealed 3 genotypes, as reported previously (40).
We observed that PXE patients and relatives carrying fetuin-A genotype 1 had significantly higher serum fetuin-A concentrations than the groups of patients and relatives carrying fetuin-A genotypes 2 and 2-1 (Table 3).
Abnormalities in several extracellular matrix components have been observed in tissues affected by PXE (26, 30, 32, 45).
To determine the link between MRP6 and the pathologic calcification in PXE, we investigated the production of fetuin-A in PXE patients.