Showing papers by "Marcus Dörr published in 2011"
Morris J. Bown1, Gregory T. Jones2, Seamus C. Harrison3, Benjamin J. Wright1 +504 more•Institutions (64)
TL;DR: This study has identified a biologically plausible genetic variant associated specifically with AAA, and it is suggested that this variant has a possible functional role in LRP1 expression.
Abstract: Abdominal aortic aneurysm (AAA) is a common cause of morbidity and mortality and has a significant heritability. We carried out a genome-wide association discovery study of 1866 patients with AAA and 5435 controls and replication of promising signals (lead SNP with a p value < 1 × 10(-5)) in 2871 additional cases and 32,687 controls and performed further follow-up in 1491 AAA and 11,060 controls. In the discovery study, nine loci demonstrated association with AAA (p < 1 × 10(-5)). In the replication sample, the lead SNP at one of these loci, rs1466535, located within intron 1 of low-density-lipoprotein receptor-related protein 1 (LRP1) demonstrated significant association (p = 0.0042). We confirmed the association of rs1466535 and AAA in our follow-up study (p = 0.035). In a combined analysis (6228 AAA and 49182 controls), rs1466535 had a consistent effect size and direction in all sample sets (combined p = 4.52 × 10(-10), odds ratio 1.15 [1.10-1.21]). No associations were seen for either rs1466535 or the 12q13.3 locus in independent association studies of coronary artery disease, blood pressure, diabetes, or hyperlipidaemia, suggesting that this locus is specific to AAA. Gene-expression studies demonstrated a trend toward increased LRP1 expression for the rs1466535 CC genotype in arterial tissues; there was a significant (p = 0.029) 1.19-fold (1.04-1.36) increase in LRP1 expression in CC homozygotes compared to TT homozygotes in aortic adventitia. Functional studies demonstrated that rs1466535 might alter a SREBP-1 binding site and influence enhancer activity at the locus. In conclusion, this study has identified a biologically plausible genetic variant associated specifically with AAA, and we suggest that this variant has a possible functional role in LRP1 expression.
189 citations
TL;DR: Low male TT concentrations are predictive of hypertension, suggesting TT as a potential biomarker of increased cardiovascular risk, and a significant inverse association of TT concentrations and blood pressure.
Abstract: Background. Studies on the relationship between testosterone concentrations and blood pressure have yielded inconsistent results. Therefore, this study investigated the prospective association of total testosterone (TT) concentrations with risk of incident hypertension and blood pressure change in 1484 men aged 20–79 years.Methods. Data from the population-based Study of Health in Pomerania, Germany, were used. Serum TT concentrations, measured by chemiluminescent enzyme immunoassays, were categorised into age-specific quartiles. Generalised Estimating Equation (GEE) models, adjusted for age, waist circumference, physical activity, smoking and alcohol consumption were specified.Results. During a median follow-up time of 5.0 years, the prevalence of hypertension increased from 50.6% to 57.1%. TT concentrations were significantly lower in men with baseline and incident hypertension. Analyses revealed that men with baseline TT concentrations in the lowest quartile had an increased risk of incident hypertensi...
70 citations
TL;DR: This study demonstrates that label-free, mass spectrometry-centered approaches can identify disease dependent alterations in the proteome from small tissue samples such as endomyocardial biopsies, which might allow better disease characterization and may be a valuable tool in potential clinical proteomic studies.
Abstract: Dilated cardiomyopathy (DCM) is characterized by contractile dysfunction leading to heart failure. The molecular changes in the human heart associated with this disease have so far mostly been addressed at the gene expression level and only a few studies have analyzed global changes in the myocardial proteome. Therefore, our objective was to investigate the changes in the proteome in patients suffering from inflammatory DCM (iDCM) and chronic viral infection by a comprehensive quantitative approach. Comparative proteomic profiling of endomyocardial biopsies (EMB) from 10 patients with iDCM (left ventricular ejection fraction <40%, symptoms of heart failure) as well as 7 controls with normal left ventricular function and histology was performed by label-free proteome analysis (LC-MS/MS). Mass spectrometric data were analyzed with the Rosetta Elucidator software package. The analysis covered a total of 485 proteins. Among the 174 proteins displaying at least a 1.3-fold change in intensity (p < 0.05), major changes were observed for mitochondrial and cytoskeletal proteins, but also metabolic pathways were affected in iDCM compared to controls. In iDCM patients, we observed decreased levels of mitochondrial proteins involved in oxidative phosphorylation and tricarboxylic acid cycle. Furthermore, deregulation of proteins of carbohydrate metabolism, the actin cytoskeleton, and extracellular matrix remodeling was observed. Proteomic observations were confirmed by gene expression data and immunohistochemistry (e.g. collagen I and VI). This study demonstrates that label-free, mass spectrometry-centered approaches can identify disease dependent alterations in the proteome from small tissue samples such as endomyocardial biopsies. Thus, this technique might allow better disease characterization and may be a valuable tool in potential clinical proteomic studies.
65 citations
TL;DR: It is demonstrated that although both approaches are based on the collection of clinical data and biosamples, different legal milieus present in the USA and Germany as well as slight differences in scientific goals have led to different 'ethical designs'.
Abstract: In this article, two different scientific approaches to personalized medicine are compared. Biorepository at Vanderbilt University (BioVU) is a genomic biorepository at Vanderbilt University Medical Center in Nashville, TN, USA. Genetic biosamples are collected from leftover clinical blood samples; medical information is derived from an electronic medical records. Greifswald Approach to Individualized Medicine is a research resource at the University of Greifswald, Germany, comprised of clinical records combined with biosamples collected for research. We demonstrate that although both approaches are based on the collection of clinical data and biosamples, different legal milieus present in the USA and Germany as well as slight differences in scientific goals have led to different ‘ethical designs’. While BioVU can successfully operate with an ‘opt-out’ mechanism, an informed consent-based ‘opt-in’ model is indispensable to allow GANI_MED to reach its scientific goals.
22 citations
TL;DR: To the Editor: There is increasing evidence that environmental factors in early pre- and post-natal life have significant impact on the development of various diseases later in adulthood.
20 citations
TL;DR: The results support current considerations that subclinical disorders of glucose metabolism measured by serum HbA(1c) are associated with subclinical cardiovascular diseases detected by FMD, especially in women.
16 citations
TL;DR: The aim of the present study was to assess the association of IGF‐I and its binding protein 3 (IGFBP‐3) with the carotid intima–media thickness (IMT) as marker of asymptomatic cardiovascular disease.
Abstract: Summary
Objective Previous studies detected associations between lower insulin-like growth factor I (IGF-I) levels and increased risk of congestive heart failure or ischaemic heart disease. The aim of the present study was to assess the association of IGF-I and its binding protein 3 (IGFBP-3) with the carotid intima–media thickness (IMT) as marker of asymptomatic cardiovascular disease.
Design and population From the population-based Study of Health in Pomerania (SHIP), a total of 2286 participants aged 45 years or older with readable ultrasound of the carotid arteries were available for the present analyses.
Methods and measurements Serum IGF-I and IGFBP-3 levels were categorized into three groups (low, moderate, high) according to the sex-specific 10th and 90th percentile. Analyses of variance (anova) and logistic regression analyses adjusted for age, waist circumference, diabetes, hypertension and creatinine clearance were performed.
Results After adjusting for confounding factors, IGF-I and the IGF-I/IGFBP-3 ratio were positively related to IMT in anova. Logistic regression analyses confirmed these findings and showed that high IGF-I levels, a high IGF-I/IGFBP-3 ratio and low IGFBP-3 levels were associated to higher odds of increased IMT.
Conclusion In conclusion, high IGF-I or high IGF-I/IGFBP-3 ratio values and low IGFBP-3 levels are associated with increased IMT. Therefore, systemic levels of the IGF axis or alterations in the balance of its components are associated with subclinical atherosclerotic disease.
15 citations
TL;DR: In current smokers, FMD is significantly associated with ventilatory efficiency, which may be interpreted as a potential clinical link between smoking and early pulmonary vasculopathy due to smoking.
Abstract: Aims: To assess the cross-sectional association between exercise capacity, gas exchange efficiency and endothelial function, as measured by flow-mediated dilation (FMD) and nitroglycerin-mediated dilation (NMD) of the brachial artery, in a large-scale population-based survey. Methods: The study population was comprised of 1416 volunteers 25 to 85 years old. Oxygen uptake at anaerobic threshold (VO2@AT), peak exercise (peakVO2) and ventilatory efficiency (VE vs. VCO2 slope and VE/VCO2@AT) were assessed on a breath-by-breath basis during incremental symptom-limited cardiopulmonary exercise. FMD and NMD measurements at rest were performed using standardised ultrasound techniques. Results: Multivariable logistic regression analyses revealed a significant association between FMD and ventilatory efficiency in current smokers but not in ex-smokers or non-smokers. There was no association between FMD and VO2@AT or peak VO2. In current smokers, for each one millimetre decrement in FMD, VE/VCO2@AT improved by -3.6 (95% CI -6.8, -0.4) in the overall population [VE vs. VCO2 slope -3.9 (-7.1, -0.6)]. These results remained robust after adjusting for all major influencing factors. Neither exercise capacity nor ventilatory efficiency was significantly associated with NMD. Conclusion: In current smokers, FMD is significantly associated with ventilatory efficiency. This result may be interpreted as a potential clinical link between smoking and early pulmonary vasculopathy due to smoking.
12 citations
TL;DR: At peak exercise performance, testosterone and SHBG levels showed no associations with V'O(2 peak) at L as well as maximal power output, even after controlling for confounding factors including age, body mass index, physical activity, and smoking.
Abstract: Testosterone exerts a widespread pattern of effects on metabolism and body composition, and interest is gaining in its correlation with physical fitness. The main focus of our study was to investigate the association of total serum testosterone and sex hormone–binding globulin (SHBG) levels on exercise capacity and maximal power output in men using a cross-sectional, population-based adult cohort. From the Study of Health in Pomerania (SHIP), 624 men age 25 to 85 years who underwent a standardized progressive incremental exercise protocol on a cycle ergometer were included in the analyses. Exercise capacity was characterized by oxygen uptake at anaerobic threshold (V′O2 at θL) and peak exercise (V′O2peak) as well as maximal power output at peak exertion. Multivariable linear regression analyses adjusted for age, sex, body mass index, physical activity, and smoking were performed. Further, linear regression analyses with cubic splines and sensitivity analyses were undertaken. At peak exercise performance, testosterone and SHBG levels showed no associations with V′O2peak, V′O2 at θL as well as maximal power output, even after controlling for confounding factors including age, body mass index, physical activity, and smoking. An adverse association between the free testosterone index and V′O2 at θL was found. Linear regression analyses with cubic splines did not change the main results. In conclusion, this is the first study focusing on the association of total serum testosterone and SHBG on exercise capacity and physical performance in healthy volunteers based on a large-scale population-based study. After adjustment for relevant influencing factors, neither total serum testosterone nor SHBG levels had any interference with peak exercise capacity, aerobic exercise capacity, or maximal power output in men.
7 citations
TL;DR: It is concluded that serum TSH levels are not associated with exercise-related blood pressure response, and similar findings were found for both subjects with T SH levels below and above the reference range, respectively.
Abstract: Background: Studies on the relation between thyroid function and exercise blood pressure (EBP) are rare and not population-based, and have yielded inconsistent results. The aim of this study was to investigate whether serum thyrotropin (TSH) levels are related to increased EBP. Methods: Cross-sectional data from 1438 subjects (711 women) aged 25–83 years without histories of cardiovascular diseases from the 5-year follow-up of the population-based Study of Health in Pomerania (SHIP-1) were analyzed. Blood pressure was measured at the 100 W stage of a symptom-limited bicycle ergometry test. Increased EBP was defined as a value above the sex- and age-specific 80th percentile of participants with serum TSH levels within the reference range (0.25–2.12 mIU/L). Results: There was no association between serum TSH levels and EBP after adjusting for sex, age, waist circumference, diabetes mellitus, smoking status, and antihypertensive medication. The odds for increased systolic EBP (odds ratio 1.24, 95% confidence...
3 citations