TY  - JOUR
A1  - Horikoshi, Momoko
A1  - Yaghootkar, Hanieh
A1  - Mook-Kanamori, Dennis O.
A1  - Sovio, Ulla
A1  - Taal, H. Rob
A1  - Hennig, Branwen J.
A1  - Bradfield, Jonathan P.
A1  - St Pourcain, Beate
A1  - Evans, David M.
A1  - Charoen, Pimphen
A1  - Kaakinen, Marika
A1  - Cousminer, Diana L.
A1  - Lehtimaki, Terho
A1  - Kreiner-Moller, Eskil
A1  - Warrington, Nicole M.
A1  - Bustamante, Mariona
A1  - Feenstra, Bjarke
A1  - Berry, Diane J.
A1  - Thiering, Elisabeth
A1  - Pfab, Thiemo
A1  - Barton, Sheila J.
A1  - Shields, Beverley M.
A1  - Kerkhof, Marjan
A1  - van Leeuwen, Elisabeth M.
A1  - Fulford, Anthony J.
A1  - Kutalik, Zoltan
A1  - Zhao, Jing Hua
A1  - den Hoed, Marcel
A1  - Mahajan, Anubha
A1  - Lindi, Virpi
A1  - Goh, Liang-Kee
A1  - Hottenga, Jouke-Jan
A1  - Wu, Ying
A1  - Raitakari, Olli T.
A1  - Harder, Marie N.
A1  - Meirhaeghe, Aline
A1  - Ntalla, Ioanna
A1  - Salem, Rany M.
A1  - Jameson, Karen A.
A1  - Zhou, Kaixin
A1  - Monies, Dorota M.
A1  - Lagou, Vasiliki
A1  - Kirin, Mirna
A1  - Heikkinen, Jani
A1  - Adair, Linda S.
A1  - Alkuraya, Fowzan S.
A1  - Al-Odaib, Ali
A1  - Amouyel, Philippe
A1  - Andersson, Ehm Astrid
A1  - Bennett, Amanda J.
A1  - Blakemore, Alexandra I. F.
A1  - Buxton, Jessica L.
A1  - Dallongeville, Jean
A1  - Das, Shikta
A1  - de Geus, Eco J. C.
A1  - Estivill, Xavier
A1  - Flexeder, Claudia
A1  - Froguel, Philippe
A1  - Geller, Frank
A1  - Godfrey, Keith M.
A1  - Gottrand, Frederic
A1  - Groves, Christopher J.
A1  - Hansen, Torben
A1  - Hirschhorn, Joel N.
A1  - Hofman, Albert
A1  - Hollegaard, Mads V.
A1  - Hougaard, David M.
A1  - Hyppoenen, Elina
A1  - Inskip, Hazel M.
A1  - Isaacs, Aaron
A1  - Jorgensen, Torben
A1  - Kanaka-Gantenbein, Christina
A1  - Kemp, John P.
A1  - Kiess, Wieland
A1  - Kilpelainen, Tuomas O.
A1  - Klopp, Norman
A1  - Knight, Bridget A.
A1  - Kuzawa, Christopher W.
A1  - McMahon, George
A1  - Newnham, John P.
A1  - Niinikoski, Harri
A1  - Oostra, Ben A.
A1  - Pedersen, Louise
A1  - Postma, Dirkje S.
A1  - Ring, Susan M.
A1  - Rivadeneira, Fernando
A1  - Robertson, Neil R.
A1  - Sebert, Sylvain
A1  - Simell, Olli
A1  - Slowinski, Torsten
A1  - Tiesler, Carla M. T.
A1  - Toenjes, Anke
A1  - Vaag, Allan
A1  - Viikari, Jorma S.
A1  - Vink, Jacqueline M.
A1  - Vissing, Nadja Hawwa
A1  - Wareham, Nicholas J.
A1  - Willemsen, Gonneke
A1  - Witte, Daniel R.
A1  - Zhang, Haitao
A1  - Zhao, Jianhua
A1  - Wilson, James F.
A1  - Stumvoll, Michael
A1  - Prentice, Andrew M.
A1  - Meyer, Brian F.
A1  - Pearson, Ewan R.
A1  - Boreham, Colin A. G.
A1  - Cooper, Cyrus
A1  - Gillman, Matthew W.
A1  - Dedoussis, George V.
A1  - Moreno, Luis A.
A1  - Pedersen, Oluf
A1  - Saarinen, Maiju
A1  - Mohlke, Karen L.
A1  - Boomsma, Dorret I.
A1  - Saw, Seang-Mei
A1  - Lakka, Timo A.
A1  - Koerner, Antje
A1  - Loos, Ruth J. F.
A1  - Ong, Ken K.
A1  - Vollenweider, Peter
A1  - van Duijn, Cornelia M.
A1  - Koppelman, Gerard H.
A1  - Hattersley, Andrew T.
A1  - Holloway, John W.
A1  - Hocher, Berthold
A1  - Heinrich, Joachim
A1  - Power, Chris
A1  - Melbye, Mads
A1  - Guxens, Monica
A1  - Pennell, Craig E.
A1  - Bonnelykke, Klaus
A1  - Bisgaard, Hans
A1  - Eriksson, Johan G.
A1  - Widen, Elisabeth
A1  - Hakonarson, Hakon
A1  - Uitterlinden, Andre G.
A1  - Pouta, Anneli
A1  - Lawlor, Debbie A.
A1  - Smith, George Davey
A1  - Frayling, Timothy M.
A1  - McCarthy, Mark I.
A1  - Grant, Struan F. A.
A1  - Jaddoe, Vincent W. V.
A1  - Jarvelin, Marjo-Riitta
A1  - Timpson, Nicholas J.
A1  - Prokopenko, Inga
A1  - Freathy, Rachel M.
T1  - New loci associated with birth weight identify genetic links between intrauterine growth and adult height and metabolism
JF  - Nature genetics
N2  - Birth weight within the normal range is associated with a variety of adult-onset diseases, but the mechanisms behind these associations are poorly understood(1). Previous genome-wide association studies of birth weight identified a variant in the ADCY5 gene associated both with birth weight and type 2 diabetes and a second variant, near CCNL1, with no obvious link to adult traits(2). In an expanded genome-wide association metaanalysis and follow-up study of birth weight (of up to 69,308 individuals of European descent from 43 studies), we have now extended the number of loci associated at genome-wide significance to 7, accounting for a similar proportion of variance as maternal smoking. Five of the loci are known to be associated with other phenotypes: ADCY5 and CDKAL1 with type 2 diabetes, ADRB1 with adult blood pressure and HMGA2 and LCORL with adult height. Our findings highlight genetic links between fetal growth and postnatal growth and metabolism.
Y1  - 2013
U6  - https://doi.org/10.1038/ng.2477
SN  - 1061-4036
VL  - 45
IS  - 1
SP  - 76
EP  - U115
PB  - Nature Publ. Group
CY  - New York
ER  - 
TY  - JOUR
A1  - Feger, Martina
A1  - Fajol, Abul
A1  - Lebedeva, Aleksandra
A1  - Meissner, Adrian
A1  - Michael, Diana
A1  - Völkl, Jakob
A1  - Alesutan, Ioana
A1  - Schleicher, Erwin
A1  - Reichetzeder, Christoph
A1  - Hocher, Berthold
A1  - Qadri, Syed M.
A1  - Lang, Florian
T1  - Effect of Carbon Monoxide Donor CORM-2 on Vitamin D-3 Metabolism
JF  - Kidney & blood pressure research : official organ of the Gesellschaft für Nephrologie
N2  - Background/Aims: Carbon monoxide (CO) interferes with cytochrome-dependent cellular functions and acts as gaseous transmitter. CO is released from CO-releasing molecules (CORM) including tricarbonyl-dichlororuthenium (II) dimer (CORM-2), molecules considered for the treatment of several disorders including vascular dysfunction, inflammation, tissue ischemia and organ rejection. Cytochrome P450-sensitive function include formation of 1,25-dihydroxyvitamin D-3 (1,25(OH)(2)D-3) by renal 25-hydroxyvitamin D-3 1-alpha-hydroxylase (Cyp27b1). The enzyme is regulated by PTH, FGF23 and klotho. 1,25(OH)(2)D-3 regulates Ca2+ and phosphate transport as well as klotho expression. The present study explored, whether CORM-2 influences 1,25(OH)(2)D-3 formation and klotho expression. Methods: Mice were treated with intravenous CORM-2 (20 mg/kg body weight). Plasma 1,25(OH)(2)D-3 and FGF23 concentrations were determined by ELISA, phosphate, calcium and creatinine concentrations by colorimetric methods, transcript levels by quantitative RT-PCR and protein expression by western blotting. Fgf23 mRNA transcript levels were further determined in rat osteosarcoma UMR106 cells without or with prior treatment for 24 hours with 20 mu M CORM-2. Results: CORM-2 injection within 24 hours significantly increased FGF23 plasma levels and decreased 1,25(OH)(2)D-3 plasma levels, renal Cyp27b1 gene expression as well as renal klotho protein abundance and transcript levels. Moreover, treatment of UMR106 cells with CORM-2 significantly increased Fgf23 transcript levels. Conclusion: CO-releasing molecule CORM-2 enhances FGF23 expression and release and decreases klotho expression and 1,25(OH)(2)D-3 synthesis.
KW  - CORM-2
KW  - 1,25-Dihydroxyvitamin D-3
KW  - Klotho
KW  - FGF23
KW  - Phosphate
KW  - Calcium
Y1  - 2013
U6  - https://doi.org/10.1159/000355730
SN  - 1420-4096
SN  - 1423-0143
VL  - 37
IS  - 4-5
SP  - 496
EP  - 505
PB  - Karger
CY  - Basel
ER  - 
TY  - JOUR
A1  - Hocher, Berthold
A1  - Oberthür, Dominik
A1  - Slowinski, Torsten
A1  - Querfeld, Uwe
A1  - Schäfer, Franz
A1  - Doyon, Anke
A1  - Tepel, Martin
A1  - Roth, Heinz J.
A1  - Grön, Hans J.
A1  - Reichetzeder, Christoph
A1  - Betzel, Christian
A1  - Armbruster, Franz Paul
T1  - Modeling of Oxidized PTH (oxPTH) and Non-oxidized PTH (n-oxPTH) Receptor Binding and Relationship of Oxidized to Non-Oxidized PTH in Children with Chronic Renal Failure, Adult Patients on Hemodialysis and Kidney Transplant Recipients
JF  - Kidney & blood pressure research : official organ of the Gesellschaft für Nephrologie
N2  - Background: The biological properties of oxidized and non-oxidized PTH are substantially different. Oxidized PTH (oxPTH) loses its PTH receptor-stimulating properties, whereas non-oxidized PTH (n-oxPTH) is a full agonist of the receptor. This was described in more than 20 well published studies in the 1970(s) and 80(s). However, PTH oxidation has been ignored during the development of PTH assays for clinical use so far. Even the nowadays used third generation assay systems do not consider oxidation of PTH. We recently developed an assay to differentiate between oxPTH and n-oxPTH. In the current study we established normal values for this assay system. Furthermore, we compare the ratio of oxPTH to n-oxPTH in different population with chronic renal failure: 620 children with renal failure stage 2-4 of the 4C study, 342 adult patients on dialysis, and 602 kidney transplant recipients. In addition, we performed modeling of the interaction of either oxPTH or n-oxPTH with the PTH receptor using biophysical structure approaches. Results: The children had the highest mean as well as maximum n-oxPTH concentrations as compared to adult patients (both patients on dialysis as well as kidney transplant recipients). The relationship between oxPTH and n-oxPTH of individual patients varied substantially in all three populations with renal impairment. The analysis of n-oxPTH in 89 healthy control subjects revealed that n-oxPTH concentrations in patient with renal failure were higher as compared to healthy adult controls (2.25-fold in children with renal failure, 1.53-fold in adult patients on dialysis, and 1.56-fold in kidney transplant recipients, respectively). Computer assisted biophysical structure modeling demonstrated, however, minor sterical- and/or electrostatic changes in oxPTH and n-oxPTH. This indicated that PTH oxidation may induce refolding of PTH and hence alters PTH-PTH receptor interaction via oxidation induced three-dimensional structure alteration of PTH. Conclusion: A huge proportion of circulating PTH measured by current state-of-the-art assay systems is oxidized and thus not biologically active. The relationship between oxPTH and n-oxPTH of individual patients varied substantially. Non-oxidized PTH concentrations are 1.5 - 2.25 fold higher in patients with renal failure as compared to health controls. Measurements of n-oxPTH may reflect the hormone status more precise. The iPTH measures describes most likely oxidative stress in patients with renal failure rather than the PTH hormone status. This, however, needs to be demonstrated in further clinical studies.
KW  - n-oxPTH
KW  - Chronic Renal Failure
KW  - Kidney Transplantation
KW  - Hemodialysis
KW  - Oxidation
KW  - PTH
KW  - Chronic Renal Failure in Children
Y1  - 2013
U6  - https://doi.org/10.1159/000350149
SN  - 1420-4096
SN  - 1423-0143
VL  - 37
IS  - 4-5
SP  - 240
EP  - 251
PB  - Karger
CY  - Basel
ER  - 
TY  - JOUR
A1  - Lu, Yong-Ping
A1  - Zeng, De-Ying
A1  - Chen, You-Peng
A1  - Liang, Xu-Jing
A1  - Xu, Jie-Ping
A1  - Huang, Si-Min
A1  - Lai, Zhi-Wei
A1  - Wen, Wang-Rong
A1  - von Websky, Karoline
A1  - Hocher, Berthold
T1  - Low birth weight is associated with lower respiratory tract infections in children with hand, foot, and mouth disease
JF  - Clinical laboratory : the peer reviewed journal for clinical laboratories and laboratories related to blood transfusion
N2  - Background: Low birth weight (LBW) might be a risk factor for acquiring lower respiratory tract infections (LRTIs) associated with disease related complications in early childhood. HFMD, a frequent viral infection in southern China, is a leading cause of lower respiratory tract infections in children. We analyzed whether LBW is a risk factor for children with HFMD to develop lower respiratory tract infections.
 Methods: A total of 298 children with HFMD, admitted to a hospital in Qingyuan city, Guangdong province, were recruited. Demographic data and clinical parameters such as serum glucose level and inflammatory markers including peripheral white blood cell count, serum C-reactive protein, and erythrocyte sedimentation rate were routinely collected on admission. Birth weight data were derived from birth records.
 Results: Mean birth weight (BW) was 167 g lower in patients with HFMD and LRTIs as compared to patients with solely HFMD (p = 0.022) and the frequency of birth weight below the tenth percentile was significantly higher in patients with HFMD and LRTIs (p = 0.002).
 Conclusions: The results of the study show that low birth weight is associated with a higher incidence of lower respiratory tract infections in young children with HFMD.
KW  - hand
KW  - foot and mouth disease (HFMD)
KW  - low birth weight (LBW)
KW  - lower respiratory tract infections (LRTIs)
KW  - pneumonia
KW  - children
Y1  - 2013
U6  - https://doi.org/10.7754/Clin.Lab.2012.120725
SN  - 1433-6510
VL  - 59
IS  - 9-10
SP  - 985
EP  - 992
PB  - Clin Lab Publ., Verl. Klinisches Labor
CY  - Heidelberg
ER  - 
TY  - JOUR
A1  - Li, Jian
A1  - Chen, You-Peng
A1  - Wang, Zi-Neng
A1  - Liu, Tie-Bin
A1  - Chen, Dan
A1  - Dong, Yun-Peng
A1  - Hocher, Berthold
T1  - A functional fetal HSD11B2[CA]n microsatellite polymorphism is associated with maternal serum cortisol concentrations in pregnant women
JF  - Kidney & blood pressure research : official organ of the Gesellschaft für Nephrologie
N2  - Background/Aims: Cortisol plays an important role during pregnancy. It controls maternal glucose metabolism and fetal development. Cortisol metabolism is partially controlled by the 11b-HSD2. This enzyme is expressed in the kidney and human placenta. The activity of the enzyme is partially controlled by functional polymorphisms: the HSD11B2[CA]n microsatellite polymorphism. The impact of this functional gene polymorphism on cortisol metabolism and potential effects on the newborn's is unknown so far. Methods: In the current prospective birth cohort study in southern Asia, we analyzed the association of the HSD11B2[CA]n microsatellite polymorphisms in 187 mothers and their newborn's on maternal and newborn's serum cortisol concentrations. Results: Using multivariable regression analyses considering known confounding ( gestational age, newborn's gender, the labor uterine contraction states and the timing during the day of blood taking), we showed that the fetal HSD11B2[CA]n microsatellite polymorphisms in the first intron was related to maternal cortisol concentration ( R2=0.26, B=96.27, p=0.007), whereas as the newborn's cortisol concentrations were independent of fetal and maternal HSD11B2[CA] n microsatellite polymorphism. Conclusions: Our study showed for the first time that the fetal HSD11B2[CA]n microsatellite polymorphism of the HSD11B2 gene in healthy uncomplicated human pregnancy is associated with maternal cortisol concentration. This indicates that fetal genes controlling cortisol metabolism may affect maternal cortisol concentration and hence physiology in healthy pregnant women.
KW  - Pregnancy
KW  - Placenta
KW  - Cortisol vertical bar metabolism
KW  - 11 beta-hydroxysteroid dehydrogenase 2
KW  - HSD11B2[CA]n polymorphism
Y1  - 2013
U6  - https://doi.org/10.1159/000355761
SN  - 1420-4096
SN  - 1423-0143
VL  - 38
IS  - 1
SP  - 132
EP  - 141
PB  - Karger
CY  - Basel
ER  - 
TY  - JOUR
A1  - Espe, Katharina M.
A1  - Raila, Jens
A1  - Henze, Andrea
A1  - Blouin, Katja
A1  - Schneider, Andreas
A1  - Schmiedeke, Daniel
A1  - Krane, Vera
A1  - Pilz, Stefan
A1  - Schweigert, Florian J.
A1  - Hocher, Berthold
A1  - Wanner, Christoph
A1  - Drechsler, Christiane
T1  - Low plasma alpha-tocopherol concentrations and adverse clinical outcomes in diabetic hemodialysis patients
JF  - Clinical journal of the American Society of Nephrology
N2  - Background and objectives Trials with the antioxidant vitamin E have failed to show benefit in the general population. Considering the different causes of death in ESRD, this study investigated the association between plasma concentrations of alpha-tocopherol and specific clinical outcomes in diabetic hemodialysis patients.
 Design, settings, participants, & measurements In 1046 diabetic hemodialysis patients (participants of the German Diabetes and Dialysis Study), alpha-tocopherol was measured in plasma by reversed-phase HPLC. By Cox regression analyses, hazard ratios were determined for prespecified end points according to baseline plasma alpha-tocopherol levels: sudden death (n=134), myocardial infarction (n=172), stroke (n=89), combined cardiovascular events (n=398), fatal infection (n=107), and all-cause mortality (n=508).
 Results Patients had a mean age of 66 8 years, and mean plasma alpha-tocopherol level was 22.8+/-9.6 mu mol/L. Levels of alpha-tocopherol were highly correlated to triglycerides (r=0.63, P<0.001). Patients in the lowest alpha-tocopherol quartile had (in unadjusted analyses) a 79% higher risk of stroke and a 31% higher risk of all-cause mortality compared with patients in the highest quartile. The associations were attenuated after adjustment for confounders (hazard ratio(stroke)=1.56, 95% confidence interval=0.75-3.25; hazard ratio(mortality)=1.22, 95% confidence interval=0.89-1.69, respectively). There was no association between alpha-tocopherol and myocardial infarction, sudden death, or infectious death.
 Conclusions Plasma alpha-tocopherol concentrations were not independently associated with cardiovascular outcomes, infectious deaths, or all-cause mortality in diabetic hemodialysis patients. The lack of association can partly be explained by a confounding influence of malnutrition, which should be considered in the planning of trials to reduce cardiovascular risk in dialysis patients.
Y1  - 2013
U6  - https://doi.org/10.2215/CJN.04880511
SN  - 1555-9041
VL  - 8
IS  - 3
SP  - 452
EP  - 458
PB  - American Society of Nephrology
CY  - Washington
ER  - 
TY  - CHAP
A1  - Hocher, Berthold
A1  - Armbruster, Franz Paul
A1  - Scholze, Alexandra
A1  - Marckmann, Peter
A1  - Reichetzeder, Christoph
A1  - Roth, Heinz Jürgen
A1  - Tepel, Martin
T1  - Non-oxidized, biological active parathyroid hormone determines motality in hemodialsysis patients
T2  - Nephrology, dialysis, transplantation
Y1  - 2013
SN  - 0931-0509
VL  - 28
SP  - 33
EP  - 33
PB  - Oxford Univ. Press
CY  - Oxford
ER  - 
TY  - INPR
A1  - Hocher, Berthold
A1  - Reichetzeder, Christoph
T1  - Vitamin D and cardiovascular risk in postmenopausal women how to translate preclinical evidence into benefit for patients
T2  - Kidney international : official journal of the International Society of Nephrology
N2  - Preclinical work indicates that calcitriol restores vascular function by normalizing the endothelial expression of cyclooxygenase-2 and thromboxane-prostanoid receptors in conditions of estrogen deficiency and thus prevents the thromboxane-prostanoid receptor activation-induced inhibition of nitric oxide synthase. Since endothelial dysfunction is a key factor in the pathogenesis of cardiovascular diseases, this finding may have an important translational impact. It provides a clear rationale to use endothelial function in clinical trials aiming to find the optimal dose of vitamin D for the prevention of cardiovascular events in postmenopausal women.
Y1  - 2013
U6  - https://doi.org/10.1038/ki.2013.139
SN  - 0085-2538
VL  - 84
IS  - 1
SP  - 9
EP  - 11
PB  - Nature Publ. Group
CY  - New York
ER  - 
TY  - JOUR
A1  - Hocher, Berthold
A1  - Sharkovska, Yuliya
A1  - Mark, Michael
A1  - Klein, Thomas
A1  - Pfab, Thiemo
T1  - The novel DPP-4 inhibitors linagliptin and BI 14361 reduce infarct size after myocardial ischemia/reperfusion in rats
JF  - International journal of cardiology
N2  - Background: Dipeptidylpeptidase-4 inhibition is reported to have beneficial effects on myocardial ischemia. Mechanisms might include a reduced degradation of stromal cell-derived factor-1 alpha with subsequent increased recruitment of circulating stem cells and/or incretin receptor-dependent pathways. This study evaluated the novel xanthine-based dipeptidylpeptidase-4 inhibitors linagliptin (BI 1356) and BI 14361 in cardiac ischemia.
 Methods: Male Wistar rats were pretreated with linagliptin or BI 14361 and subjected to ligation of the left anterior descending coronary artery for 30 min.
 Results: Dipeptidylpeptidase-4 inhibition significantly reduced the infarct size after 7 days (-27.7%, p<0.05) and 8 weeks (-18.0%, p<0.05). There was a significantly improved maximum rate of left ventricular pressure decline (dP/dt min) in linagliptin-treated animals 8 weeks after ischemia/reperfusion. Apart from that, treatment did not improve cardiac function as determined by echocardiography and cardiac catheterization. Immunohistological staining revealed an increased number of cells positive for stromal cell-derived factor-1 alpha, CXCR-4 and CD34 within and around the infarcted area of BI 14361-treated animals.
 Conclusions: Linagliptin and BI 14361 are able to reduce infarct size after myocardial ischemia. The immunohistological findings support the hypothesis that dipeptidylpeptidase-4 inhibition via reduced cleavage of stromal cell-derived factor-1 alpha might lead to an enhanced recruitment of CXCR-4+ circulating progenitor cells.
KW  - Dipeptidylpeptidase-4
KW  - Stromal cell-derived factor-1
KW  - Cardiac ischemia/reperfusion
KW  - Myocardial ischemia
KW  - Infarct size
KW  - Rats
Y1  - 2013
U6  - https://doi.org/10.1016/j.ijcard.2011.12.007
SN  - 0167-5273
VL  - 167
IS  - 1
SP  - 87
EP  - 93
PB  - Elsevier
CY  - Clare
ER  - 
TY  - CHAP
A1  - Sharkovska, Y.
A1  - Pohl, K. K.
A1  - Hocher, Berthold
A1  - Dschietzig, T.
T1  - Cardiac expression of relaxin and its receptor RXFP1 in rats with
 renovascular hypertension
T2  - EUROPEAN HEART JOURNAL
Y1  - 2013
SN  - 0195-668X
SN  - 1522-9645
VL  - 34
IS  - 10
SP  - 1056
EP  - 1056
PB  - OXFORD UNIV PRESS
CY  - OXFORD
ER  -