title: Gender-specific plasma proteomic biomarkers in patients with Anderson-Fabry disease.
abstract: OBJECTIVE
  Anderson-Fabry disease (AFD) is an important X-linked metabolic disease resulting in progressive end-organ involvement, with cardiac disease being the dominant determinant of survival in a gender-dependent manner. Recent epidemiological screening for AFD suggests the prevalence is much higher than previously recognized, with estimates of 1:3000. Our aim was to discover novel plasma biomarker signatures in adult patients with AFD.
  
  
  RESULTS
  We used an unbiased proteomic screening approach to discover novel plasma biomarker signatures. In the discovery cohort of 46 subjects, 14 healthy controls and 32 patients with AFD, we used a mass spectrometry iTRAQ proteomic approach followed by multiple reaction monitoring (MRM) assays to identify biomarkers. Of the 38 protein groups discovered by iTRAQ, 18 already had existing MRM assays. Based on MRM, we identified an eight-protein biomarker panel (22 kDa protein, afamin, α1 antichymotrypsin, apolipoprotein E, β-Ala His dipeptidase, haemoglobin α-2, isoform 1 of sex hormone-binding globulin, and peroxiredoxin 2) that was very specific and sensitive for male AFD patients. In female AFD patients, we identified a nine-marker panel of proteins with only three proteins, apolipoprotein E, haemoglobin α-2, and peroxiredoxin 2, common to both genders, suggesting a gender-specific alteration in plasma biomarkers in patients with AFD. The biomarkers were validated in plasma samples from 48 subjects using MRM, and they performed inferiorly in patients with heart failure.
  
  
  CONCLUSIONS
  We have identified gender-specific plasma protein biomarker panels that are specific and sensitive for the AFD phenotype. The gender-specific panels offer important insight into potential differences in pathophysiology and prognosis between males and females with AFD.
authors.affiliation: Centre of Excellence for Prevention of Organ Failure (PROOF Centre), Vancouver, Canada.
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Hollander
authors.forename: Darlene L Y
authors.initials: DL
authors.lastname: Dai
authors.forename: Brendan N
authors.initials: BN
authors.lastname: Putko
authors.forename: Haran
authors.initials: H
authors.lastname: Yogasundaram
authors.forename: Janet E
authors.initials: JE
authors.lastname: Wilson-McManus
authors.forename: Richard B
authors.initials: RB
authors.lastname: Thompson
authors.forename: Aneal
authors.initials: A
authors.lastname: Khan
authors.forename: Michael L
authors.initials: ML
authors.lastname: West
authors.forename: Bruce M
authors.initials: BM
authors.lastname: McManus
authors.forename: Gavin Y
authors.initials: GY
authors.lastname: Oudit
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001241:Aspirin / Q000008:administration & dosage; D015415:Biomarkers / Q000097:blood*; D001798:Blood Proteins / Q000378:metabolism*; D002561:Cerebrovascular Disorders / Q000097:blood*; D003430:Cross-Sectional Studies; D000795:Fabry Disease / Q000097:blood*; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D040901:Proteomics / Q000379:methods*; D012737:Sex Factors; D055815:Young Adult; D000519:alpha-Galactosidase / Q000235:genetics
chemical_list: D015415:Biomarkers; D001798:Blood Proteins; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; C576330:GLA protein, human; D000519:alpha-Galactosidase; D001241:Aspirin
keywords: Anderson-Fabry disease; Biomarker; Cardiomyopathy; Proteomics