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  • 1
    Online Resource
    Online Resource
    Data_Sheet_2.xlsx
    Frontiers Media SA ; 2022
    In:  Frontiers in Cardiovascular Medicine Vol. 8 ( 2022-1-14)
    Details
    In: Frontiers in Cardiovascular Medicine, Frontiers Media SA, Vol. 8 ( 2022-1-14)
    Abstract: Serum calciprotein particle maturation time (T 50 ), a measure of vascular calcification propensity, is associated with cardiovascular morbidity and mortality. We aimed to identify genetic loci associated with serum T 50 and study their association with cardiovascular disease and mortality. Methods: We performed a genome-wide association study of serum T 50 in 2,739 individuals of European descent participating in the Prevention of REnal and Vascular ENd-stage Disease (PREVEND) study, followed by a two-sample Mendelian randomization (MR) study to examine causal effects of T 50 on cardiovascular outcomes. Finally, we examined associations between T 50 loci and cardiovascular outcomes in 8,566 community-dwelling participants in the Rotterdam study. Results: We identified three independent genome-wide significant single nucleotide polymorphism (SNPs) in the AHSG gene encoding fetuin-A: rs4917 ( p = 1.72 × 10 −101 ), rs2077119 ( p = 3.34 × 10 −18 ), and rs9870756 ( p = 3.10 × 10 −8 ), together explaining 18.3% of variation in serum T 50 . MR did not demonstrate a causal effect of T 50 on cardiovascular outcomes in the general population. Patient-level analyses revealed that the minor allele of rs9870756, which explained 9.1% of variation in T 50 , was associated with a primary composite endpoint of all-cause mortality or cardiovascular disease [odds ratio (95% CI) 1.14 (1.01–1.28)] and all-cause mortality alone [1.14 (1.00–1.31)] . The other variants were not associated with clinical outcomes. In patients with type 2 diabetes or chronic kidney disease, the association between rs9870756 and the primary composite endpoint was stronger [OR 1.40 (1.06–1.84), relative excess risk due to interaction 0.54 (0.01–1.08)]. Conclusions: We identified three SNPs in the AHSG gene that explained 18.3% of variability in serum T 50 levels. Only one SNP was associated with cardiovascular outcomes, particularly in individuals with type 2 diabetes or chronic kidney disease.
    Type of Medium: Online Resource
    ISSN: 2297-055X
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.3389/fcvm.2021.809717
    DOI: 10.3389/fcvm.2021.809717.s001
    DOI: 10.3389/fcvm.2021.809717.s002
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2781496-8
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  • 2
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    Online Resource
    DataSheet_1.pdf
    Frontiers Media SA ; 2023
    In:  Frontiers in Immunology Vol. 13 ( 2023-1-4)
    Details
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 13 ( 2023-1-4)
    Abstract: Kidney transplant recipients (KTRs) have an impaired immune response after vaccination against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Iron deficiency (ID) may adversely affect immunity and vaccine efficacy. We aimed to investigate whether ferric carboxymaltose (FCM) treatment improves humoral and cellular responses after SARS-CoV-2 vaccination in iron-deficient KTRs. Methods We randomly assigned 48 iron-deficient KTRs to intravenous FCM (1-4 doses of 500mg with six-week intervals) or placebo. Co-primary endpoints were SARS-CoV-2-specific anti-Receptor Binding Domain (RBD) Immunoglobulin G (IgG) titers and T-lymphocyte reactivity against SARS-CoV-2 at four weeks after the second vaccination with mRNA-1273 or mRNA-BNT162b2. Results At four weeks after the second vaccination, patients receiving FCM had higher plasma ferritin and transferrin saturation ( P & lt;0.001 vs. placebo) and iron (P=0.02). However, SARS-CoV-2-specific anti-RBD IgG titers (FCM: 66.51 [12.02-517.59] BAU/mL; placebo: 115.97 [68.86-974.67] BAU/mL, P =0.07) and SARS-CoV-2-specific T-lymphocyte activation (FCM: 93.3 [0.85-342.5] IFN-ɣ spots per 10 6 peripheral blood mononuclear cells (PBMCs), placebo: 138.3 [0.0-391.7] IFN-ɣ spots per 10 6 PBMCs, P =0.83) were not significantly different among both arms. After the third vaccination, SARS-CoV-2-specific anti-RBD IgG titers remained similar between treatment groups (P=0.99). Conclusions Intravenous iron supplementation efficiently restored iron status but did not improve the humoral or cellular immune response against SARS-CoV-2 after three vaccinations.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    URL: Article
    URL: Article
    DOI: 10.3389/fimmu.2022.1017178
    DOI: 10.3389/fimmu.2022.1017178.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2606827-8
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  • 3
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    Diagnostic Yield of Next-Generation Sequencing in Patients With Chronic Kidney Disease of Unknown Etiology
    Frontiers Media SA ; 2019
    In:  Frontiers in Genetics Vol. 10 ( 2019-12-13)
    Details
    In: Frontiers in Genetics, Frontiers Media SA, Vol. 10 ( 2019-12-13)
    Type of Medium: Online Resource
    ISSN: 1664-8021
    URL: Article
    DOI: 10.3389/fgene.2019.01264
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2019
    detail.hit.zdb_id: 2606823-0
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  • 4
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    Editorial: Genetics of Kidney Diseases
    Frontiers Media SA ; 2020
    In:  Frontiers in Genetics Vol. 11 ( 2020-4-3)
    Details
    In: Frontiers in Genetics, Frontiers Media SA, Vol. 11 ( 2020-4-3)
    Type of Medium: Online Resource
    ISSN: 1664-8021
    URL: Article
    DOI: 10.3389/fgene.2020.00305
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2020
    detail.hit.zdb_id: 2606823-0
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  • 5
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    Association of Endogenous Erythropoietin Levels and Iron Status With Cognitive Functioning in the General Population
    Frontiers Media SA ; 2022
    In:  Frontiers in Aging Neuroscience Vol. 14 ( 2022-4-8)
    Details
    In: Frontiers in Aging Neuroscience, Frontiers Media SA, Vol. 14 ( 2022-4-8)
    Abstract: Emerging data suggest that erythropoietin (EPO) promotes neural plasticity and that iron homeostasis is needed to maintain normal physiological brain function. Cognitive functioning could therefore be influenced by endogenous EPO levels and disturbances in iron status. Objective To determine whether endogenous EPO levels and disturbances in iron status are associated with alterations in cognitive functioning in the general population. Materials and Methods Community-dwelling individuals from the Prevention of Renal and Vascular End-Stage Disease (PREVEND) study, a general population-based cohort in Groningen, Netherlands, were surveyed between 2003 and 2006. Additionally, endogenous EPO levels and iron status, consisting of serum iron, transferrin, ferritin, and transferrin saturation were analyzed. Cognitive function was assessed by scores on the Ruff Figural Fluency Test (RFFT), as a reflection of executive function, and the Visual Association Test (VAT), as a reflection of associative memory. Results Among 851 participants (57% males; mean age 60 ± 13 years), higher endogenous EPO levels were independently associated with an improved cognitive function, reflected by RFFT scores (ß = 0.09, P = 0.008). In multivariable backward linear regression analysis, EPO levels were among the most important modifiable determinants of RFFT scores (ß = 0.09, P = 0.002), but not of VAT scores. Of the iron status parameters, only serum ferritin levels were inversely associated with cognitive function, reflected by VAT scores, in multivariable logistic regression analysis (odds ratio, 0.77; 95% confidence interval 0.63–0.95; P = 0.02 for high performance on VAT, i.e., ≥11 points). No association between iron status parameters and RFFT scores was identified. Conclusion The findings suggest that endogenous EPO levels and serum ferritin levels are associated with specific cognitive functioning tests in the general population. Higher EPO levels are associated with better RFFT scores, implying better executive function. Serum ferritin levels, but not other iron status parameters, were inversely associated with high performance on the VAT score, implying a reduced ability to create new memories and recall recent past. Further research is warranted to unravel underlying mechanisms and possible benefits of therapeutic interventions.
    Type of Medium: Online Resource
    ISSN: 1663-4365
    URL: Article
    DOI: 10.3389/fnagi.2022.862856
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2558898-9
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  • 6
    Online Resource
    Online Resource
    Data_Sheet_1.docx
    Frontiers Media SA ; 2022
    In:  Frontiers in Cardiovascular Medicine Vol. 9 ( 2022-11-14)
    Details
    In: Frontiers in Cardiovascular Medicine, Frontiers Media SA, Vol. 9 ( 2022-11-14)
    Abstract: Levels of N-terminal pro B-type natriuretic peptide (NT-proBNP), a marker of heart failure and cardiovascular risk, are generally higher in women than men. We explored whether iron biomarkers mediate sex differences in NT-proBNP levels. Methods We included 5,343 community-dwelling individuals from the Prevention of Renal and Vascular Endstage Disease study. With linear regression analyses, we investigated the association of sex and iron biomarkers with NT-proBNP levels, independent of adjustment for potential confounders. The assessed iron biomarkers included ferritin, transferrin saturation (TSAT), hepcidin, and soluble transferrin receptor (sTfR). Next, we performed mediation analyses to investigate to which extent iron biomarkers influence the association between sex and NT-proBNP. Results Of the included 5,343 participants, the mean standard deviation age was 52.2 ± 11.6 years and 52% were females. After adjustment for potential confounders, women compared to men, had higher NT-proBNP (β = 0.31; 95%CI = 0.29, 0.34), but lower ferritin (β = –0.37; 95%CI = –0.39, –0.35), hepcidin (β = –0.22, 95%CI = –0.24, –0.20), and TSAT (β = –0.07, 95% CI = –0.08, –0.06). Lower ferritin (β = –0.05, 95%CI = –0.08, –0.02), lower hepcidin (β = –0.04, 95%CI = –0.07, –0.006), and higher TSAT (β = 0.07; 95%CI = 0.01, 0.13) were associated with higher NT-proBNP. In mediation analyses, ferritin and hepcidin explained 6.5 and 3.1% of the association between sex and NT-proBNP, respectively, while TSAT minimally suppressed (1.9%) this association. Conclusion Our findings suggest that iron biomarkers marginally explain sex differences in levels of NT-proBNP. Future studies are needed to explore causality and potential mechanisms underlying these pathways.
    Type of Medium: Online Resource
    ISSN: 2297-055X
    URL: Article
    URL: Article
    DOI: 10.3389/fcvm.2022.897148
    DOI: 10.3389/fcvm.2022.897148.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2781496-8
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  • 7
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    The modified base J is the target for a novelDNA-binding protein in kinetoplastid protozoans
    Wiley ; 1999
    In:  The EMBO Journal Vol. 18, No. 22 ( 1999-11-15), p. 6573-6581
    Details
    In: The EMBO Journal, Wiley, Vol. 18, No. 22 ( 1999-11-15), p. 6573-6581
    Type of Medium: Online Resource
    ISSN: 0261-4189 , 1460-2075
    URL: Article
    DOI: 10.1093/emboj/18.22.6573
    RVK:
    WA 15000
    Language: Unknown
    Publisher: Wiley
    Publication Date: 1999
    detail.hit.zdb_id: 1467419-1
    detail.hit.zdb_id: 586044-1
    SSG: 12
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