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Gene polymorphisms in the heme degradation pathway and outcome of severe human sepsis
SepNet - German Competence Network Sepsis

Abstract (Expand)

Heme and its breakdown products CO, Fe, and bilirubin are being recognized as signaling molecules or even therapeutic agents, but also exert adverse effects when released at high concentrations. … Manipulating the pathway confers protection in rodent sepsis models via both control of free heme and formation of its first and higher-order products. Thus, regulatory elements present in human heme oxygenase 1 (HMOX1) and biliverdin reductases (BLVRA/B) genes might impact outcome. We tested whether a highly polymorphic (GT)n microsatellite and single-nucleotide polymorphisms in HMOX1 and BLVRA/B genes are associated with outcome of sepsis. Two cohorts (n = 430 and 398 patients) with severe sepsis were screened for single-nucleotide polymorphisms and/or the microsatellite by fragment length analysis and genotyping techniques. Heme oxygenase 1 plasma levels were determined in additional patients with severe sepsis (n = 92) by enzyme-linked immunosorbent assay. Based on mean Sepsis-related Organ Failure Assessment scores, patients homozygous for rs2071746 A allele or medium length (GT)n microsatellites of HMOX1 showed higher 28-day mortality (P = 0.047 and P = 0.033) in one cohort compared with other genotypes, whereas 90-day mortality rates showed no association. The T allele was less frequently observed in both cohorts than would be expected according to Hardy-Weinberg equilibrium. Heme oxygenase 1 plasma levels were elevated in septic patients, independent of the genotype. Single-nucleotide polymorphisms within BLVRA/B showed no association with outcome. Short (GT)n repeats that are in linkage disequilibrium with the T allele of rs2071746 in HMOX1 are associated with favorable outcome, whereas no association with gene variants of BLVRA/B, involved in the generation of higher-order metabolites, was noticed.

Authors: Christoph Sponholz, Klaus Huse, Marcel Kramer, Evangelos J. Giamarellos-Bourboulis, Ralf A. Claus, Anna Kern, Christoph Engel, Evelyn Kuhnt, Michael Kiehntopf, Christina Routsi, Vassiliki Mylona, Iraklis Tsangaris, Stefan H. Heinemann, Konrad Reinhart, Matthias Platzer, Michael Bauer

Date Published: 2012

Publication Type: Journal article

Human Diseases: disease by infectious agent

Association of rs2069459 in the CDK5 gene with dyslexia in a German cohort
Genetical Statistics and Systems Biology

Abstract

Not specified

Authors: Jana Burkhardt, Holger Kirsten, Heidrun Holland, Wolfgang Krupp, Carolin Ligges, Elfi Quente, Johannes Boltze, Peter Ahnert, Arndt Wilcke

Date Published: 2012

Publication Type: Journal article

Differential allelic expression of IL13 and CSF2 genes associated with asthma
Genetical Statistics and Systems Biology

Abstract (Expand)

An important area of genetic research is the identification of functional mechanisms in polymorphisms associated with diseases. A highly relevant functional mechanism is the influence of polymorphisms … on gene expression levels (differential allelic expression, DAE). The coding single nucleotide polymorphisms (SNPs) CSF2(rs25882) and IL13(rs20541) have been associated with asthma. In this work, we investigated whether the mRNA expression levels of CSF2 or IL13 were correlated with these SNPs. Samples were analyzed by mass spectrometry-based quantification of gene expression. Both SNPs influenced gene expression levels (CSF2(rs25882): p(overall) = 0.008 and p(DAE samples) = 0.00006; IL13(rs20541): p(overall) = 0.059 and p(DAE samples) = 0.036). For CSF2, the expression level was increased by 27.4% (95% CI: 18.5%-35.4%) in samples with significant DAE in the presence of one copy of risk variant CSF2(rs25882-T). The average expression level of IL13 was increased by 29.8% (95% CI: 3.1%-63.4%) in samples with significant DAE in the presence of one copy of risk variant IL13(rs20541-A). Enhanced expression of CSF2 could stimulate macrophages and neutrophils during inflammation and may be related to the etiology of asthma. For IL-13, higher expression could enhance the functional activity of the asthma-associated isoform. Overall, the analysis of DAE provides an efficient approach for identifying possible functional mechanisms that link disease-associated variants with altered gene expression levels.

Authors: Jana Burkhardt, Holger Kirsten, Grit Wolfram, Elfi Quente, Peter Ahnert

Date Published: 2012

Publication Type: Journal article

Association study of a functional genetic variant in KIAA0319 in German dyslexics
Genetical Statistics and Systems Biology

Abstract

Not specified

Authors: Holger Kirsten, Arndt Wilcke, Carolin Ligges, Johannes Boltze, Peter Ahnert

Date Published: 2012

Publication Type: Journal article

Pre-operative Tei Index does not predict left ventricular function immediately after mitral valve repair
Genetical Statistics and Systems Biology

Abstract (Expand)

Echocardiographic assessment of systolic left ventricular (LV) function in patients with severe mitral regurgitation (MR) undergoing mitral valve (MV) repair can be challenging because the measurement … of ejection fraction (EF) or fractional area change (FAC) in pathological states is of questionable value. The aim of our study was to evaluate the usefulness of the pre-operative Tei Index in predicting left ventricular EF or FAC immediately after MV repair. One hundred and thirty patients undergoing MV repair with sinus rhythm pre- and post-operatively were enrolled in this prospective study. Twenty-six patients were excluded due to absence of sinus rhythm post-operatively. Standard transesophageal examination (IE 33, Philips, Netherlands) was performed before and after cardiopulmonary bypass according to the guidelines of the ASE/SCA. FAC was determined in the transgastric midpapillary short-axis view. LV EF was measured in the midesophageal four- and two-chamber view. For calculation of the Tei Index, the deep transgastric and the midesophageal four-chamber view were used. Statistical analysis was performed with SPSS 17.0. values are expressed as mean with standard deviation. LV FAC and EF decreased significantly after MV repair (FAC: 56\pm12% vs. 50\pm14%, P\textless0.001; EF: 58\pm11 vs. 50\pm12\textgreek’E P\textless0.001). The Tei Index decreased from 0.66\pm0.23 before MV repair to 0.41\pm0.19 afterwards (P\textless0.001). No relationship between pre-operative Tei Index and post-operative FAC or post-operative EF were found (FAC: r=-0.061, P=0.554; EF: r=-0.29, P=0.771). Conclusion: Pre-operative Tei Index is not a good predictor for post-operative FAC and EF in patients undergoing MV repair.

Authors: Chirojit Mukherjee, Steffen Groeger, Maurice Hogan, Markus Scholz, Udo X. Kaisers, Joerg Ender

Date Published: 2012

Publication Type: Journal article

Intrathecal morphine is superior to intravenous PCA in patients undergoing minimally invasive cardiac surgery
Genetical Statistics and Systems Biology

Abstract (Expand)

Aim of our study was to evaluate the beneficial effect of low dose intrathecal morphine on postoperative analgesia, over the use of intravenous patient controlled anesthesia (PCA), in patients undergoing … fast track anesthesia during minimally invasive cardiac surgical procedures. A randomized controlled trial was undertaken after approval from local ethical committee. Written informed consent was obtained from 61 patients receiving mitral or tricuspid or both surgical valve repair in minimal invasive technique. Patients were assigned randomly to 2 groups. Group 1 received general anesthesia and intravenous patient controlled analgesia (PCA) pump with Piritramide (GA group). Group 2 received a single shot of intrathecal morphine (1.5 \textgreekmg/kg body weight) prior to the administration of general anesthesia (ITM group). Site of puncture was confined to lumbar (L1-2 or L2-3) intrathecal space. The amount of intravenous piritramide used in post anesthesia care unit (PACU) and the first postoperative day was defined as primary end point. Secondary end points included: time for tracheal extubation, pain and sedation scores in PACU upto third postoperative day. For statistical analysis Mann-Whitney-U Test and Fishers exact test (SPSS) were used. We found that the demand for intravenous opioids in PACU was significantly reduced in ITM group (P \textless0.001). Pain scores were significantly decreased in ITM group until second postoperative day (P \textless0.01). There was no time delay for tracheal extubation in ITM group, and sedation scores did not differ in either group. We conclude that low dose single shot intrathecal morphine provides adequate postoperative analgesia, reduces the intravenous opioid consumption during the early postoperative period and does not defer early extubation.

Authors: Chirojit Mukherjee, Eva Koch, Joergen Banusch, Markus Scholz, Udo X. Kaisers, Joerg Ender

Date Published: 2012

Publication Type: Journal article

Biomathematische Modellierung von Therapiewirkungen bei Lymphomerkrankungen - Ein Beitrag zur Medizinischen Systembiologie
Genetical Statistics and Systems Biology

Abstract

Not specified

Author: Markus Scholz

Date Published: 2012

Publication Type: Journal article

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