Role of serum fetuin-A, a major inhibitor of systemic calcification, in pseudoxanthoma elasticum.
BACKGROUND
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.


METHODS
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.


RESULTS
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 <0.0001)]. Serum fetuin-A was higher in female PXE patients with cardiovascular involvement than in the corresponding male group (P <0.05). The fetuin-A polymorphism frequencies did not differ among PXE patients, family members, and blood donors.


CONCLUSIONS
A deficiency of multidrug resistance-associated protein 6 leads to alteration of circulating substrates, e.g., inhibitors of calcification as fetuin-A, leading to progressive mineralization of elastic fibers in PXE.
Hendig
Doris
D
Institut für Laboratoriums- und Transfusionsmedizin, Herz- und Diabeteszentrum Nordrhein-Westfalen, Universitätsklinik der Ruhr-Universität Bochum, Bad Oeynhausen, Germany.
Schulz
Veronika
V
Arndt
Marius
M
Szliska
Christiane
C
Kleesiek
Knut
K
Götting
Christian
C
D001798:Blood Proteins / Q000032:analysis / Q000235:genetics / Q000502:physiology; D002114:Calcinosis / Q000209:etiology / Q000235:genetics*; D004247:DNA / Q000032:analysis; D004252:DNA Mutational Analysis; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005858:Germany; D006801:Humans; D008297:Male; D008875:Middle Aged; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics*; D009154:Mutation; D010375:Pedigree; D012150:Polymorphism, Restriction Fragment Length; D011561:Pseudoxanthoma Elasticum / Q000097:blood* / Q000150:complications / Q000235:genetics; D060749:alpha-2-HS-Glycoprotein
D001798:Blood Proteins; D004247:DNA; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D060749:alpha-2-HS-Glycoprotein; C102029:ABCC6 protein, human; C556354:AHSG protein, human