HIF1A and MIF as potential predictive mRNA biomarkers of pre-eclampsia: a longitudinal prospective study in high risk population
-
Silvia Galbiati
,
Annalisa Inversetti
Abstract
Background: Pre-eclampsia (PE) is a hypertensive multisystem disorder, causing significant fetal-maternal mortality and morbidity worldwide. This study aims to define possible longitudinal predictive mRNA markers involved in the main pathogenic pathways of PE: inflammation [macrophage migration inhibitory factor (MIF)], hypoxia and oxidative stress [hypoxia inducible factor 1-α subunit (HIF1A) and β-site APP-cleaving enzyme-2 (BACE2)] and endothelial dysfunction [endoglin (ENG), fms-related tyrosine kinase-1 (FLT1) and vascular endothelial growth factor (VEGF)].
Methods: Peripheral blood was collected from 33 singleton pregnancies characterized by a high cardiovascular profile risk sampled consecutively at 6–16; 17–23; 24–30; 31–34; ≥35 weeks followed by the Obstetrics and Gynecology Unit of the San Raffaele Hospital in Milan. A real-time quantitative PCR reaction was performed on plasma RNA.
Results: Of the 33 women enrolled, nine developed PE. Until 23 weeks HIF1A was significantly higher in women who later developed PE compared to women who did not (p=0.049 and p=0.012 in the first and second blood collection). In the third time interval MIF (p=0.0005), FLT1 (p=0.024), ENG (p=0.0034) and BACE2 (p=0.044) appeared to be significantly increased while HIF1A was elevated even from 24 week onwards but not reaching the statistical significance. In the fourth time interval ENG mRNA still remained increased (p=0.037).
Conclusions: HIF1A, marker of hypoxia and oxidative stress, and MIF, marker of inflammation, seemed to be the most promising RNA markers, suggesting that hypoxia, principally, and inflammation may play an important role in PE pathogenesis.
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©2015 by De Gruyter
Articles in the same Issue
- Frontmatter
- Editorial
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- Review
- Thyroglobulin measurement by highly sensitive assays: focus on laboratory challenges
- Opinion Paper
- Possible role of fructosamine 3-kinase genotyping for the management of diabetic patients
- EFLM Original Article
- Compliance of blood sampling procedures with the CLSI H3-A6 guidelines: An observational study by the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) working group for the preanalytical phase (WG-PRE)
- Genetics and Molecular Diagnostics
- Quantitative-fluorescent-PCR versus full karyotyping in prenatal diagnosis of common chromosome aneuploidies in southern Spain
- HIF1A and MIF as potential predictive mRNA biomarkers of pre-eclampsia: a longitudinal prospective study in high risk population
- General Clinical Chemistry and Laboratory Medicine
- Evidence of Crohn’s disease-related anti-glycoprotein 2 antibodies in patients with celiac disease
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- Automated immunoassays for the autoantibodies to carbamylated or citrullinated telopeptides of type I and II collagens
- Relevance of correction for drift and day-to-day variation in cystatin C measurement: a post-hoc analysis of the PREVEND cohort, with independent replication in the ESTHER cohort
- Laboratory utilization improvement through a computer-aided algorithm developed with general practitioners
- Quantitation of 1α,25-dihydroxyvitamin D by LC-MS/MS using solid-phase extraction and fixed-charge derivitization in comparison to immunoextraction
- Reference Values and Biological Variations
- Establishment of trimester-specific thyroid stimulating hormone and free thyroxine reference interval in pregnant Chinese women using the Beckman Coulter UniCel™ DxI 600
- Cancer Diagnostics
- Expression of vascular endothelial factor-A, gelatinases (MMP-2, MMP-9) and TIMP-1 in uterine leiomyomas
- Influence of ABO type on global coagulation assay results: effect of coagulation factor VIII
- Diabetes
- Benchmarking by HbA1c in a national diabetes quality register – does measurement bias matter?
- Comparing HbA1c, fasting and 2-h plasma glucose for screening for abnormal glucose regulation in patients undergoing coronary angiography
- Erroneous HbA1c measurements in the presence of β-thalassemia and common Chinese hemoglobin variants
- Using the likelihood ratio to evaluate allowable total error – an example with glycated hemoglobin (HbA1c)
- Two novel haemoglobin variants that affect haemoglobin A1c measurement by ion-exchange chromatography
- Analytical performances of the D-100TM hemoglobin testing system (Bio-Rad) for HbA1c assay
- Letters to the Editors
- Glycation rate of haemoglobins S, C, D, E, J and G, and analytical interference on the measurement of HbA1c with affinity chromatography and capillary electrophoresis
- Hemoglobin Valme HBB:c.124T>G: a new hemoglobin variant with diminished oxygen affinity causes interference in hemoglobin A1c measurement in an automated ion-exchange HPLC method
- Hemoglobin A1c reported in units and diagnostic cut-offs in relation to the international recommendations
- Hemoglobin measurements in samples containing hemoglobin-based oxygen carriers
- Serologic false-positive reactions for syphilis in children of allergic purpura
- Exploration of the pre-analytical stability of β-lactam antibiotics in plasma and blood – implications for therapeutic drug monitoring and pharmacokinetic studies
- Fungal contamination of hyaluronidase solution mimicking fungal joint infection: a preanalytical pitfall in synovial fluid analysis
- Stroke and inherited thrombophilia in a Tunisian girl with sickle cell anemia
- Faecal haemoglobin concentrations do vary across geography as well as with age and sex: ramifications for colorectal cancer screening
Articles in the same Issue
- Frontmatter
- Editorial
- New trends in the long and puzzling history of HbA1c
- Review
- Thyroglobulin measurement by highly sensitive assays: focus on laboratory challenges
- Opinion Paper
- Possible role of fructosamine 3-kinase genotyping for the management of diabetic patients
- EFLM Original Article
- Compliance of blood sampling procedures with the CLSI H3-A6 guidelines: An observational study by the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) working group for the preanalytical phase (WG-PRE)
- Genetics and Molecular Diagnostics
- Quantitative-fluorescent-PCR versus full karyotyping in prenatal diagnosis of common chromosome aneuploidies in southern Spain
- HIF1A and MIF as potential predictive mRNA biomarkers of pre-eclampsia: a longitudinal prospective study in high risk population
- General Clinical Chemistry and Laboratory Medicine
- Evidence of Crohn’s disease-related anti-glycoprotein 2 antibodies in patients with celiac disease
- Myocardial interleukin-6 in the setting of left ventricular mechanical assistance: relation with outcome and C-reactive protein
- Different methods to estimate serum free cortisol: a comparison during cortisol tetracosactide testing
- Automated immunoassays for the autoantibodies to carbamylated or citrullinated telopeptides of type I and II collagens
- Relevance of correction for drift and day-to-day variation in cystatin C measurement: a post-hoc analysis of the PREVEND cohort, with independent replication in the ESTHER cohort
- Laboratory utilization improvement through a computer-aided algorithm developed with general practitioners
- Quantitation of 1α,25-dihydroxyvitamin D by LC-MS/MS using solid-phase extraction and fixed-charge derivitization in comparison to immunoextraction
- Reference Values and Biological Variations
- Establishment of trimester-specific thyroid stimulating hormone and free thyroxine reference interval in pregnant Chinese women using the Beckman Coulter UniCel™ DxI 600
- Cancer Diagnostics
- Expression of vascular endothelial factor-A, gelatinases (MMP-2, MMP-9) and TIMP-1 in uterine leiomyomas
- Influence of ABO type on global coagulation assay results: effect of coagulation factor VIII
- Diabetes
- Benchmarking by HbA1c in a national diabetes quality register – does measurement bias matter?
- Comparing HbA1c, fasting and 2-h plasma glucose for screening for abnormal glucose regulation in patients undergoing coronary angiography
- Erroneous HbA1c measurements in the presence of β-thalassemia and common Chinese hemoglobin variants
- Using the likelihood ratio to evaluate allowable total error – an example with glycated hemoglobin (HbA1c)
- Two novel haemoglobin variants that affect haemoglobin A1c measurement by ion-exchange chromatography
- Analytical performances of the D-100TM hemoglobin testing system (Bio-Rad) for HbA1c assay
- Letters to the Editors
- Glycation rate of haemoglobins S, C, D, E, J and G, and analytical interference on the measurement of HbA1c with affinity chromatography and capillary electrophoresis
- Hemoglobin Valme HBB:c.124T>G: a new hemoglobin variant with diminished oxygen affinity causes interference in hemoglobin A1c measurement in an automated ion-exchange HPLC method
- Hemoglobin A1c reported in units and diagnostic cut-offs in relation to the international recommendations
- Hemoglobin measurements in samples containing hemoglobin-based oxygen carriers
- Serologic false-positive reactions for syphilis in children of allergic purpura
- Exploration of the pre-analytical stability of β-lactam antibiotics in plasma and blood – implications for therapeutic drug monitoring and pharmacokinetic studies
- Fungal contamination of hyaluronidase solution mimicking fungal joint infection: a preanalytical pitfall in synovial fluid analysis
- Stroke and inherited thrombophilia in a Tunisian girl with sickle cell anemia
- Faecal haemoglobin concentrations do vary across geography as well as with age and sex: ramifications for colorectal cancer screening
