NCBI Summary:
This gene encodes a preproprotein, which is processed to yield both alpha and beta chains, which subsequently combine as a tetramer to produce haptoglobin. Haptoglobin functions to bind free plasma hemoglobin, which allows degradative enzymes to gain access to the hemoglobin, while at the same time preventing loss of iron through the kidneys and protecting the kidneys from damage by hemoglobin. Mutations in this gene and/or its regulatory regions cause ahaptoglobinemia or hypohaptoglobinemia. This gene has also been linked to diabetic nephropathy, the incidence of coronary artery disease in type 1 diabetes, Crohn's disease, inflammatory disease behavior, primary sclerosing cholangitis, susceptibility to idiopathic Parkinson's disease, and a reduced incidence of Plasmodium falciparum malaria. The protein encoded also exhibits antimicrobial activity against bacteria. A similar duplicated gene is located next to this gene on chromosome 16. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2014]
General function
Extracellular binding protein
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Cellular localization
Secreted
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others123
Ovarian function
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Validation of proteomic biomarkers previously found to be differentially expressed in women with Polycystic Ovary Syndrome: a cross-sectional study. Haoula Z 2014 et al.
Abstract Objectives: The aim of this study was to independently validate proteomic biomarkers previously reported to be differentially expressed in women with Polycystic Ovary Syndrome (PCOS) compared with controls. This study focused on plasma proteomic biomarkers. Methods: This was a cross-sectional study at the University of Nottingham, in which samples from 30 PCOS and 30 control women were analysed by Western blotting. Results: Mean abundance ratios from Western blots of plasma total haptoglobin and haptoglobin beta proteins were 1.25 (CI 1.11-1.4) and 1.24 (CI 1.04-1.44). The mean abundance ratio from the blots of alpha-2 macroglobulin was however 1.05 (CI, 1-1.1). The mean PCOS/control BMI ratio was 1.18 (CI 1.17-1.20). There was no correlation between PCOS/control BMI ratio and alpha-2 macroglobulin, total haptoglobin and haptoglobin beta abundance ratios. There was also no correlation between PCOS/control insulin ratio and alpha-2 macroglobulin, total haptoglobin and haptoglobin beta abundance ratios. Conclusions: Total haptoglobin and haptoglobin beta chain protein abundance was found to be elevated in women with PCOS compared with controls. We were unable to confirm decreased alpha-2 macroglobulin levels as reported in a previous study. Independent validation studies are required to validate early promising proteomic biomarkers in PCOS.
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Expression regulated by
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Ovarian localization
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Follicle stages
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Phenotypes
PCO (polycystic ovarian syndrome)
Mutations
1 mutations
Species: human
Mutation name: None
type: naturally occurring fertility: subfertile Comment: Proteomic Analysis of Plasma in the Polycystic Ovary Syndrome Identifies Novel Markers Involved in Iron Metabolism, Acute-Phase Response, and Inflammation. Insenser M et al. 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.