Proteomic analysis of plasma in the polycystic ovary syndrome identifies novel markers involved in iron metabolism, acute-phase response, and inflammation

J Clin Endocrinol Metab. 2010 Aug;95(8):3863-70. doi: 10.1210/jc.2010-0220. Epub 2010 May 19.

Abstract

Context: Hypothesis-free approaches such as proteomic analysis may identify novel biomarkers for disease.

Objective: The objective of the study was to compare the plasma proteome of patients presenting with the polycystic ovary syndrome (PCOS) with that of women without hyperandrogenism.

Design: This was a case-control study.

Settings: The study was conducted at an academic hospital.

Patients: Patients included 12 PCOS patients and 12 women without hyperandrogenism.

Interventions: Interventions included basal blood sampling.

Main outcome measures: Two-dimensional difference in-gel electrophoresis, matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry, Western blot, and ELISA analyses were measured.

Results: Two-dimensional difference in-gel electrophoresis and matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry analyses identified haptoglobin beta-chain and alpha2-macroglobulin as proteins underexpressed in PCOS samples, whereas transferrin and kappa-free light chain were overexpressed. We were able to confirm only the underexpression of haptoglobin beta-chain in subsequent Western blot and ELISA analyses.

Conclusions: Proteomic analysis of plasma from PCOS patients revealed changes in protein expression in several acute-phase response proteins including isoforms of plasma haptoglobin, alpha2-macroglobulin, and transferrin and in kappa-free light chain. In addition to their role as inflammatory markers, some of these molecules play major roles in iron metabolism, further suggesting that iron metabolism and low-grade chronic inflammation may be involved in the pathogenesis of insulin-resistant disorders such as PCOS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute-Phase Reaction / blood*
  • Adult
  • Biomarkers / blood
  • Blotting, Western
  • Case-Control Studies
  • Electrophoresis, Gel, Two-Dimensional
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Haptoglobins / metabolism
  • Humans
  • Hyperandrogenism / metabolism
  • Iron / metabolism*
  • Polycystic Ovary Syndrome / metabolism*
  • Proteomics
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

Substances

  • Biomarkers
  • HP protein, human
  • Haptoglobins
  • Iron