title: Decreased serum antioxidant capacity in patients with Wilson disease is associated with neurological symptoms.
abstract: OBJECTIVE
  Wilson disease (WD) is an inherited disorder of copper disposition caused by an ATP7B transporter gene mutation, leading to copper accumulation in predisposed tissues. In addition to a genetic predisposition, other factors are likely to contribute to its clinical manifestation. The aim of the study was to assess whether oxidative stress affects the phenotypic manifestation of WD.
  
  
  METHODS
  In 56 patients with WD (29 men; 26 with the hepatic form, 22 with the neurologic form, and eight asymptomatic; mean age 38.5 ± 12 years), total serum antioxidant capacity (TAC) and inflammatory parameters (hs-CRP, IL-1β, IL-2, IL-6, IL-10, and TNF-α) were analyzed and related to the clinical manifestation, and mutations of the ATP7B gene. The control group for the TAC and inflammatory parameters consisted of 50 age- and gender-matched healthy individuals.
  
  
  RESULTS
  WD patients had a significantly lower TAC (p < 0.00001), lower IL-10 levels (p = 0.039), as well as both higher IL-1β (p = 0.019) and IL-6 (p = 0.005) levels compared to the control subjects. TNF-α, hs-CRP, and IL-2 did not differ from the controls. Patients with the neurological form of WD had a significantly lower TAC than those with the hepatic form (p < 0.001). In addition, the lower TAC was associated with the severity of the neurological symptoms (p = 0.02). No relationship between the inflammatory parameters and clinical symptoms was found.
  
  
  CONCLUSIONS
  Data from our study suggest that the increased oxidative stress contributes significantly to the clinical manifestation of WD; as a lower TAC is associated with the neurological symptoms in WD patients.
authors.affiliation: First Faculty of Medicine, 4th Department of Internal Medicine, Charles University in Prague, Prague, Czech Republic. bruha@cesnet.cz
authors.forename: Radan
authors.initials: R
authors.lastname: Bruha
authors.forename: Libor
authors.initials: L
authors.lastname: Vitek
authors.forename: Zdenek
authors.initials: Z
authors.lastname: Marecek
authors.forename: Lenka
authors.initials: L
authors.lastname: Pospisilova
authors.forename: Sona
authors.initials: S
authors.lastname: Nevsimalova
authors.forename: Pavel
authors.initials: P
authors.lastname: Martasek
authors.forename: Jaromir
authors.initials: J
authors.lastname: Petrtyl
authors.forename: Petr
authors.initials: P
authors.lastname: Urbanek
authors.forename: Alena
authors.initials: A
authors.lastname: Jiraskova
authors.forename: Ivana
authors.initials: I
authors.lastname: Malikova
authors.forename: Martin
authors.initials: M
authors.lastname: Haluzik
authors.forename: Peter
authors.initials: P
authors.lastname: Ferenci
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics*; D000328:Adult; D000975:Antioxidants / Q000378:metabolism*; D027682:Cation Transport Proteins / Q000235:genetics*; D003300:Copper / Q000378:metabolism; D000073840:Copper-Transporting ATPases; D005260:Female; D020022:Genetic Predisposition to Disease; D006527:Hepatolenticular Degeneration / Q000097:blood*; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009422:Nervous System Diseases / Q000097:blood*; D018384:Oxidative Stress
chemical_list: D000975:Antioxidants; D027682:Cation Transport Proteins; D053583:Interleukin-1beta; D015850:Interleukin-6; D016753:Interleukin-10; D003300:Copper; D000251:Adenosine Triphosphatases; C000612464:ATP7B protein, human; D000073840:Copper-Transporting ATPases