Role of Serum Fetuin-A, a Major Inhibitor of Systemic Calcification, in Pseudoxanthoma Elasticum

Pseudoxanthoma elasticum (PXE) is a hereditary disorder of the connective tissue affecting the skin, retina, and cardiovascular system and characterized by progressive calcification of abnormal and fragmented elastic fibers in the extracellular matrix. The aim of the present study was to investigate the association of fetuin-A, a major systemic inhibitor of calcification, with PXE. Fetuin-A was measured by quantitative sandwich enzyme immunoassay in sera from 110 German patients with PXE, 53 unaffected first-degree family members, and 80 healthy blood donors. We determined the distribution of the fetuin-A polymorphisms c.742C>T (p.T248M) and c.766C>G (p.T256S) in these same 3 groups. The occurrences of the frequent ABCC6 gene mutations c.3421C>T (p.R1141X) and c.EX23_EX29del were also assessed. Serum fetuin-A concentrations in male and female PXE patients were lower than in unaffected first-degree relatives and controls [mean (SD) concentrations, 0.55 (0.11) g/L in patients; 0.70 (0.23) g/L in relatives; and 0.80 (0.23) g/L in controls (P