title: Haptoglobin phenotype modifies serum iron levels and the effect of smoking on Parkinson disease risk.
abstract: BACKGROUND
  Haptoglobin is a hemoglobin-binding protein that exists in three functionally different phenotypes, and haptoglobin phenotype 2-1 has previously been associated with Parkinson disease (PD) risk, with mechanisms not elucidated. Some evidence is emerging that low levels of serum iron may increase PD risk. In this study we investigated whether PD patients have lower serum iron and ferritin than controls, and whether this is dependent on haptoglobin phenotype. We also investigated the effect of Hp phenotype as a modifier of the effect of smoking on PD risk.
  
  
  METHODS
  The study population consisted of 128 PD patients and 226 controls. Serum iron, ferritin, and haptoglobin phenotype were determined, and compared between PD cases and controls. Stratified analysis by haptoglobin phenotype was performed to determine effect of haptoglobin phenotype on serum iron parameter differences between PD cases and controls and to investigate its role in the protective effect of smoking on PD risk.
  
  
  RESULTS
  PD cases had lower serum iron than controls (83.28 ug/100 ml vs 94.00 ug/100 ml, p 0.006), and in particular among subjects with phenotype 2-1. The protective effect of smoking on PD risk resulted stronger in subjects with phenotype 1-1 and 2-2, and weakest among subjects with phenotype 2-1. Ferritin levels were higher in PD cases than controls among subjects of White ethnicity.
  
  
  CONCLUSIONS
  Our results report for the first time that the haptoglobin phenotype may be a contributor of iron levels abnormalities in PD patients. The mechanisms for these haptoglobin-phenotype specific effects will have to be further elucidated.
authors.affiliation: Bastyr University Research Institute, Kenmore, WA, USA. Electronic address: pcostamallen@bastyr.edu.
authors.forename: Paola
authors.initials: P
authors.lastname: Costa-Mallen
authors.affiliation: Veterans Affairs Puget Sound Health Care System, Seattle, WA, USA; Department of Neurology, University of Washington School of Medicine, Seattle, WA, USA.
authors.forename: Cyrus P
authors.initials: CP
authors.lastname: Zabetian
authors.affiliation: Booth Gardner Parkinson's Care Center, Evergreen Health, Kirkland, WA, USA.
authors.forename: Pinky
authors.initials: P
authors.lastname: Agarwal
authors.affiliation: Department of Neurology, University of Washington School of Medicine, Seattle, WA, USA.
authors.forename: Shu-Ching
authors.initials: SC
authors.lastname: Hu
authors.affiliation: Veterans Affairs Puget Sound Health Care System, Seattle, WA, USA.
authors.forename: Dora
authors.initials: D
authors.lastname: Yearout
authors.affiliation: Veterans Affairs Puget Sound Health Care System, Seattle, WA, USA; Department of Neurology, University of Washington School of Medicine, Seattle, WA, USA.
authors.forename: Ali
authors.initials: A
authors.lastname: Samii
authors.affiliation: Lou Ruvo Center for Brain Health, Neurological Institute, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: James B
authors.initials: JB
authors.lastname: Leverenz
authors.affiliation: Virginia Mason Medical Center, Seattle, WA, USA.
authors.forename: John W
authors.initials: JW
authors.lastname: Roberts
authors.affiliation: University of California San Diego, Department of Family & Preventive Medicine, La Jolla, USA.
authors.forename: Harvey
authors.initials: H
authors.lastname: Checkoway
mesh_terms: D000367:Age Factors; D000368:Aged; D000704:Analysis of Variance; D005260:Female; D005293:Ferritins / Q000097:blood; D006242:Haptoglobins / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D007501:Iron / Q000097:blood*; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010300:Parkinson Disease / Q000097:blood* / Q000208:ethnology / Q000235:genetics*; D010641:Phenotype; D012307:Risk Factors; D012737:Sex Factors; D012907:Smoking / Q000097:blood*
chemical_list: D006242:Haptoglobins; D005293:Ferritins; D007501:Iron
keywords: Haptoglobin phenotype; Idiopathic Parkinson disease; Serum ferritin; Serum iron; Tobacco smoking