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(1 - 4 of 4)
Whole-exome sequencing identifies SLC52A1 and ZNF106 variants as novel genetic risk factors for (early) multiple-organ failure in acute pancreatitis
Berg, F.F. van den; Issa, Y.; Vreijling, J.P.; Lerch, M.M.; Weiss, F.U.; Besselink, M.G.; ... ; Santvoort, H.C. van 2021
Whole-exome sequencing identifies SLC52A1 and ZNF106 variants as novel genetic risk factors for (early) multiple-organ failure in acute pancreatitis
Article / Letter to editor
open access
Objective: The aim of this study was to identify genetic variants associated with early multiple organ failure (MOF) in acute pancreatitis.Summary background data: MOF is a life-threatening... Show moreObjective: The aim of this study was to identify genetic variants associated with early multiple organ failure (MOF) in acute pancreatitis.Summary background data: MOF is a life-threatening complication of acute pancreatitis, and risk factors are largely unknown, especially in early persistent MOF. Genetic risk factors are thought to enhance severity in complex diseases such as acute pancreatitis.Methods: A 2-phase study design was conducted. First, we exome sequenced 9 acute pancreatitis patients with early persistent MOF and 9 case-matched patients with mild edematous pancreatitis (phenotypic extremes) from our initial Dutch cohort of 387 patients. Secondly, 48 candidate variants that were overrepresented in MOF patients and 10 additional variants known from literature were genotyped in a replication cohort of 286 Dutch and German patients.Results: Exome sequencing resulted in 161,696 genetic variants, of which the 38,333 nonsynonymous variants were selected for downstream analyses. Of these, 153 variants were overrepresented in patients with multiple-organ failure, as compared with patients with mild acute pancreatitis. In total, 58 candidate variants were genotyped in the joined Dutch and German replication cohort. We found the rs12440118 variant of ZNF106 to be overrepresented in patients with MOF (minor allele frequency 20.4% vs 11.6%, Padj = 0.026). Additionally, SLC52A1 rs346821 was found to be overrepresented (minor allele frequency 48.0% vs 42.4%, Padj = 0.003) in early MOF. None of the variants known from literature were associated.Conclusions: This study indicates that SLC52A1, a riboflavin plasma membrane transporter, and ZNF106, a zinc finger protein, may be involved in disease progression toward (early) MOF in acute pancreatitis.Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved. Show less
Diurnal rhythms in the white adipose tissue transcriptome are disturbed in obese individuals with type 2 diabetes compared with lean control individuals
Stenvers, D.J.; Jongejan, A.; Atiqi, S.; Vreijling, J.P.; Limonard, E.J.; Endert, E.; ... ; Bisschop, P.H. 2019
Diurnal rhythms in the white adipose tissue transcriptome are disturbed in obese individuals with type 2 diabetes compared with lean control individuals
Article / Letter to editor
metadata only
Aims/hypothesisAnimal studies have indicated that disturbed diurnal rhythms of clock gene expression in adipose tissue can induce obesity and type 2 diabetes. The importance of the circadian timing... Show moreAims/hypothesisAnimal studies have indicated that disturbed diurnal rhythms of clock gene expression in adipose tissue can induce obesity and type 2 diabetes. The importance of the circadian timing system for energy metabolism is well established, but little is known about the diurnal regulation of (clock) gene expression in obese individuals with type 2 diabetes. In this study we aimed to identify key disturbances in the diurnal rhythms of the white adipose tissue transcriptome in obese individuals with type 2 diabetes.MethodsIn a case-control design, we included six obese individuals with type 2 diabetes and six healthy, lean control individuals. All participants were provided with three identical meals per day for 3days at zeitgeber time (ZT, with ZT 0:00 representing the time of lights on) 0:30, 6:00 and 11:30. Four sequential subcutaneous abdominal adipose tissue samples were obtained, on day 2 at ZT 15:30, and on day 3 at ZT 0:15, ZT 5:45 and ZT 11:15. Gene expression was measured using RNA sequencing.ResultsThe core clock genes showed reduced amplitude oscillations in the individuals with type 2 diabetes compared with the healthy control individuals. Moreover, in individuals with type 2 diabetes, only 1.8% (303 genes) of 16,818 expressed genes showed significant diurnal rhythmicity, compared with 8.4% (1421 genes) in healthy control individuals. Enrichment analysis revealed a loss of rhythm in individuals with type 2 diabetes of canonical metabolic pathways involved in the regulation of lipolysis. Enrichment analysis of genes with an altered mesor in individuals with type 2 diabetes showed decreased activity of the translation initiating pathway EIF2 signaling'. Individuals with type 2 diabetes showed a reduced diurnal rhythm in postprandial glucose concentrations.Conclusions/interpretationDiurnal clock and metabolic gene expression rhythms are decreased in subcutaneous adipose tissue of obese individuals with type 2 diabetes compared with lean control participants. Future investigation is needed to explore potential treatment targets as identified by our study, including clock enhancement and induction of EIF2 signalling.Data availabilityThe raw sequencing data and supplementary files for rhythmic expression analysis and Ingenuity Pathway Analysis have been deposited in NCBI Gene Expression Omnibus (GEO series accession number GSE104674). Show less
Cis D4Z4 repeat duplications associated with facioscapulohumeral muscular dystrophy type 2
Lemmers, R.J.L.F.; Vliet, P.J. van der; Vreijling, J.P.; Henderson, D.; Stoep, N. van der; Voermans, N.; ... ; Maarel, S.M. van der 2018
Cis D4Z4 repeat duplications associated with facioscapulohumeral muscular dystrophy type 2
Article / Letter to editor
metadata only
Systemic inhibition of the membrane attack complex impedes neuroinflammation in chronic relapsing experimental autoimmune encephalomyelitis
Michailidou, I.; Jongejan, A.; Vreijling, J.P.; Georgakopoulou, T.; Wissel, M.B. de; Wolterman, R.A.; ... ; Baas, F. 2018
Systemic inhibition of the membrane attack complex impedes neuroinflammation in chronic relapsing experimental autoimmune encephalomyelitis
Article / Letter to editor
open access