Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    Keywords: GENE ; VARIANTS ; HEALTH ; HEART-FAILURE ; SOCIETY ; susceptibility loci ; CORONARY-ARTERY-DISEASE ; Myocarditis ; HLA-C ; CARDIOLOGY
    Abstract: Aims Dilated cardiomyopathy (DCM) is one of the leading causes for cardiac transplantations and accounts for up to one-third of all heart failure cases. Since extrinsic and monogenic causes explain only a fraction of all cases, common genetic variants are suspected to contribute to the pathogenesis of DCM, its age of onset, and clinical progression. By a large-scale case-control genome-wide association study we aimed here to identify novel genetic risk loci for DCM. Methods and reuslts Applying a three-staged study design, we analysed more than 4100 DCM cases and 7600 controls. We identified and successfully replicated multiple single nucleotide polymorphism on chromosome 6p21. In the combined analysis, the most significant association signal was obtained for rs9262636 (P = 4.90 x 10(-9)) located in HCG22, which could again be replicated in an independent cohort. Taking advantage of expression quantitative trait loci (eQTL) as molecular phenotypes, we identified rs9262636 as an eQTL for several closely located genes encoding class I and class II major histocompatibility complex heavy chain receptors. Conclusion The present study reveals a novel genetic susceptibility locus that clearly underlines the role of genetically driven, inflammatory processes in the pathogenesis of idiopathic DCM.
    Type of Publication: Journal article published
    PubMed ID: 23853074
    Signatur Availability
    BibTip Others were also interested in ...
  • 2
    Keywords: EXPRESSION ; COLORECTAL-CANCER ; MYOCARDIAL-INFARCTION ; COLONY-STIMULATING FACTOR ; CORONARY-HEART-DISEASE ; ATHEROSCLEROSIS RISK ; GENOME-WIDE ASSOCIATION ; LYMPHOCYTE ; CHARGE CONSORTIUM ; DIFFERENTIAL LEUKOCYTE COUNT ; GENETIC-VARIANTS ; PROSTATE-CANCER SUSCEPTIBILITY
    Abstract: White blood cell (WBC) count is a common clinical measure from complete blood count assays, and it varies widely among healthy individuals. Total WBC count and its constituent subtypes have been shown to be moderately heritable, with the heritability estimates varying across cell types. We studied 19,509 subjects from seven cohorts in a discovery analysis, and 11,823 subjects from ten cohorts for replication analyses, to determine genetic factors influencing variability within the normal hematological range for total WBC count and five WBC subtype measures. Cohort specific data was supplied by the CHARGE, HeamGen, and INGI consortia, as well as independent collaborative studies. We identified and replicated ten associations with total WBC count and five WBC subtypes at seven different genomic loci (total WBC count-6p21 in the HLA region, 17q21 near ORMDL3, and CSF3; neutrophil count-17q21; basophil count- 3p21 near RPN1 and C3orf27; lymphocyte count-6p21, 19p13 at EPS15L1; monocyte count-2q31 at ITGA4, 3q21, 8q24 an intergenic region, 9q31 near EDG2), including three previously reported associations and seven novel associations. To investigate functional relationships among variants contributing to variability in the six WBC traits, we utilized gene expression- and pathways-based analyses. We implemented gene-clustering algorithms to evaluate functional connectivity among implicated loci and showed functional relationships across cell types. Gene expression data from whole blood was utilized to show that significant biological consequences can be extracted from our genome-wide analyses, with effect estimates for significant loci from the meta-analyses being highly corellated with the proximal gene expression. In addition, collaborative efforts between the groups contributing to this study and related studies conducted by the COGENT and RIKEN groups allowed for the examination of effect homogeneity for genome-wide significant associations across populations of diverse ancestral backgrounds.
    Type of Publication: Journal article published
    PubMed ID: 21738480
    Signatur Availability
    BibTip Others were also interested in ...
  • 3
    Abstract: Recent studies strongly support an association of the nicotinic acetylcholine receptor gene cluster CHRNA5-CHRNA3-CHRNB4 with nicotine dependence (ND). However, the precise genotype-phenotype relationship is still unknown. Clinical and epidemiological data on smoking behavior raise the possibility that the relevant gene variants may indirectly contribute to the development of ND by affecting cognitive performance in some smokers who consume nicotine for reasons of "cognition enhancement." Here, we tested seven single nucleotide polymorphisms (SNPs) rs684513, rs637137, rs16969968, rs578776, rs1051730, rs3743078, rs3813567 from the CHRNA5-CHRNA3-CHRNB4 gene cluster for association with ND, measures of cognitive performance and gene expression. As expected, we found all SNPs being associated with ND in three independent cohorts (KORA, NCOOP, ESTHER) comprising 5,561 individuals. In an overlapping sample of 2,186 subjects we found three SNPs (rs16969968, rs1051730, rs3743078) being associated with cognitive domains from the Wechsler-Adult-Intelligence Scale (WAIS-R)-most notably in the performance subtest "object assembly" and the verbal subtest "similarities." In a refined analysis of a subsample of 485 subjects, two of these three SNPs (rs16969968, rs1051730) were associated with n-back task performance/Continuous Performance Test. Furthermore, two CHRNA5 risk alleles (rs684513, rs637137) were associated with CHRNA5 mRNA expression levels in whole blood in a subgroup of 190 subjects. We here report for the first time an association of CHRNA5-CHRNA3-CHRNB4 gene variants with cognition possibly mediating in part risk for developing ND. The observed phenotype-genotype associations may depend on altered levels of gene expression.
    Type of Publication: Journal article published
    PubMed ID: 20886544
    Signatur Availability
    BibTip Others were also interested in ...
  • 4
    ISSN: 1432-0584
    Keywords: Hematopoiesis ; Stem cells ; Mathematical model ; Hypoxia ; Posthypoxia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A previously described mathematical model of the hematopoietic stem cell system has been extended to permit a detailed understanding of the data during and after hypoxia. The model includes stem cells, erythroid and granuloid progenitors and precursors. Concerning the intramedullary feedback mechanisms two basic assumptions are made: 1) The fraction “a” of CFU-S in active cell cycle is regulated. Reduced cell densities of CFU-S, progenitors or precursors lead to an accelerated stem cell cycling. Enlarged cell densities suppress cycling. 2) The self renewal probability “p” of CFU-S is also regulated. The normal steady state is described by p=0.5, indicating that on statistical average each dividing mother stem cell is replaced by one daughter stem cell, while the second differentiates. Diminished cell densities of CFU-S or enlarged densities of progenitors and precursors induce a more intensive self renewal (p〉0.5), such that the stem cell number increases. The self renewal probability declines (p〈0.5) if too many CFU-S or too few progenitors and precursors are present. The model reproduces bone marrow data for CFU-S, BFU-E, CFU-C, CFU-E, 59 Fe-uptake and nucleated cells in hypoxia and posthypoxia. Although the ratio of differentiation into the erythroid and granuloid cell lines is kept constant in the model, a changing ratio of CFU-E and CFU-C results. The model suggests that stem cells and progenitor cells are regulated by a regulatory interference of erythropoiesis and granulopoiesis.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 5
    ISSN: 1600-0668
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Architecture, Civil Engineering, Surveying , Medicine
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Journal of pest science 30 (1957), S. 183-185 
    ISSN: 1612-4766
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Zusammenfassung Einleitend wird ein Verzeichnis von Termitenarten tropischer Länder gegeben, welche nach Europa verschleppt wurden, aber hier im Freiland nicht lebensfähig sind. Zootermopsis angusticollis (Hagen) aus dem westlichen Nordamerika, eine Feuchtholztermite, wurde in frisch importierten Stammabschnitten 1955 in England in Douglasie, 1956 in Hamburg in Lawsonzypresse gefunden. —Reticulitermes flavipes (Kollar), die in Hamburg eingebürgerte Gelbfußtermite, konnte in Mannheim in zahlreichen Kolonien in den äußeren Borkenschichten vonPinus echinata-Stammabschnitten festgestellt werden. Die betreffenden Hölzer waren am 29. Nov. 1956 in Norfolk, Virginia, verladen worden und am 4. Jan. 1957 angekommen. In Mannheim wurde der Einschleppungsweg bis zu seinem Endpunkte sichtbar: Durch das Wegbringen der abgeschälten Borke als Brennstoff in die Wohnhäuser, ist eine direkte Einpflanzung des Schädlings denkbar. —Im mittleren Rheingebiete muß die Gelbfußtermite, an geheimgehaltenem Orte eingebürgert sein. Die nachgewiesenen neuen Termitenpunkte, umspannnend den weiten Landraum Mittelrhein-Hallein-Berlin-Hamburg, sind eine ernste, kein optimistisches Zuwarten rechtfertigende Warnung, wie drohend in Wirklichkeit die wirtschaftliche Gefahr der Ausbreitung dieses Schädlings in Mitteleuropa geworden ist, der angesiedelt, seiner Bekämpfung fast unüberwindliche Schwierigkeiten entgegensetzt. Die Erwartung, nur warme Landschaften seien der Einbürgerung zugänglich, wird entkräftet durch den im Nordalpenzuge gelegenen volksstarken Halleiner Fundpunkt. Einen weiteren neuen Zug bringt die EntdeckungSchmidt's in das gängige Bild, daß die Gelbfußtermite zu einer primären Schadtätigkeit in Sträuchern und Bäumen befähigt ist, in einer Art, die vielleicht sogar im Walde von Bedeutung werden könnte.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 7
    Electronic Resource
    Electronic Resource
    Oxford, UK : Munksgaard International Publishers
    Indoor air 15 (2005), S. 0 
    ISSN: 1600-0668
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Architecture, Civil Engineering, Surveying , Medicine
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 8
    ISSN: 1600-0668
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Architecture, Civil Engineering, Surveying , Medicine
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 9
    Electronic Resource
    Electronic Resource
    Oxford, UK : Munksgaard International Publishers
    Allergy 59 (2004), S. 0 
    ISSN: 1398-9995
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background:  The study of partners can help to understand the impact of environmental influences on the development of allergies. We aimed to test the hypothesis that subjects whose partners have hay fever are at increased risk for the same disease and that the risk increases with the time subjects live together with an affected partner.Methods:  A nested unmatched case–control study was performed in a random sample of 4261 inhabitants, aged 25–74 years, of the City of Augsburg, Germany, and two adjacent counties. Using standardized computer-assisted face-to-face interviews, we determined the risk of doctor-diagnosed hay fever in subjects who lived together with a partner having the same disease as opposed to subjects living with an unaffected partner. Furthermore, the risk of doctor-diagnosed hay fever depending on the time the subjects had lived together with an affected partner was calculated.Results:  After adjustment for age, sex, parental predisposition and social status, the risk of hay fever was more than double in subjects who lived together with a partner having the same disease (odds ratio, ORadj., 2.41; 95% confidence interval, CI, 1.48–3.92). If subjects lived together with an affected partner, the risk of developing the disease increased with the time the partners lived together (1–11 years, OR 1; 12–23 years, OR 1.8; 24–35 years, OR 7.4; 36–54 years, OR 13.7).Conclusion:  The risk of developing hay fever is significantly elevated in subjects who live together with a partner having the same disease. The risk further increases with the time the partners live together. This points to important shared environmental influences or behaviours and raises speculations on a transmissible cause.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 10
    Electronic Resource
    Electronic Resource
    Oxford, UK : Munksgaard International Publishers
    Allergy 58 (2003), S. 0 
    ISSN: 1398-9995
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background: Recent cross-sectional studies suggested that highest sensitization prevalences occur with moderate cat allergen exposures. We aimed to assess the impact of moderate levels of second-hand cat allergen exposure on the incidence of specific sensitization and wheezing in the framework of a birth cohort study. Therefore we restricted our analysis to infants without a cat at home since birth.Methods: At infant's age 3 months, cat allergen levels were measured in the mattress dust of 1840 families without cats. At age 2 years, serum IgE specific to Fel d 1 was analyzed. Incidence of wheezing apart from respiratory infection was assessed by questionnaire. Logistic regression models were used to calculate adjusted odds ratios (OR) for the association between second-hand cat allergen exposure and health outcomes.Results: Until age 2 years, 13 of 1301 infants (1%) were sensitized to cat allergen and 56 of 1492 infants (4%) had ever-wheezing without infection. Early exposure to second-hand cat allergen levels ≥ 1 µg/g dust increased substantially the risk for specific sensitization to Fel d 1 (OR 10.9, 95% CI 3.4–35.0) and ever-wheeze without infection (OR 2.0, 95% CI 1.1–3.9) at age 2 years.Conclusions: Second-hand exposure to cat allergen in homes without cats is detrimental in terms of allergy development in infants.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...