| Title: | Identification of novel loci involved in adalimumab response in Crohn’s disease patients using integration of genome profiling and isoform-level immune-cell deconvoluted transcriptome profiling of colon tissue |
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| Authors: | ID Gorenjak, Mario (Author)
ID Jezernik, Gregor (Author)
ID Krušič, Martina (Author)
ID Skok, Pavel (Author)
ID Potočnik, Uroš (Author) |
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| Files: |  Gorenjak_2022_Identification_of_Novel_Loci_Involved.pdf (1,65 MB)
MD5: FB8DF46C9A5621E82619426E782CB8F4
 https://doi.org/10.3390/pharmaceutics14091893
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| Language: | English |
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| Work type: | Scientific work |
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| Typology: | 1.01 - Original Scientific Article |
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| Organization: | MF - Faculty of Medicine
FKKT - Faculty of Chemistry and Chemical Engineering
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| Abstract: | Crohn’s disease is a consequence of dysregulated inflammatory response to the host’s microbiota. Although anti-TNF treatment improves the quality of the patient’s life, a large proportion of patients lose response to the treatment. The past decade of research has led to a continuum of studies showcasing the heterogeneity of anti-TNF response; thus, the aim of the present study was to dissect transcriptome-wide findings to transcript isoform specific levels and combine the analyses with refined information of immune cell landscapes in colon tissue, and subsequently select promising candidates using gene ontology and genomic integration. We enrolled Slovenian Crohn’s disease patients who were naïve with respect to adalimumab treatment. We performed colon tissue RNA sequencing and peripheral blood mononuclear cell DNA genotyping with a subsequent contemporary integrative approach to combine immune cell deconvoluted isoform transcript specific transcriptome analysis, gene ontology layering and genomic data. We identified nine genes (MACF1, CTSE, HDLBP, HSPA9, HLA-DMB, TAP2, LGMN, ANAPC11, ACP5) with 15 transcripts and 16 variants involved in the adalimumab response. Our study identified loci, some of which were previously shown to contribute to inflammatory bowel disease susceptibility, as novel loci involved in adalimumab response in Crohn’s disease patients. |
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| Keywords: | Crohn’s disease, adalimumab, transcriptome, isoforms, deconvolution |
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| Publication status: | Published |
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| Publication version: | Version of Record |
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| Submitted for review: | 10.08.2022 |
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| Article acceptance date: | 02.09.2022 |
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| Publication date: | 07.09.2022 |
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| Publisher: | MDPI |
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| Year of publishing: | 2022 |
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| Number of pages: | Str. 1-16 |
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| Numbering: | Letn. 14, št. 9, št. članka 1893 |
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| PID: | 20.500.12556/DKUM-91257  |
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| UDC: | 616.3 |
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| ISSN on article: | 1999-4923 |
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| COBISS.SI-ID: | 120609795 |
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| DOI: | 10.3390/pharmaceutics14091893 |
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| Copyright: | © 2022 by the authors |
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| Publication date in DKUM: | 05.12.2024 |
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| Views: | 174 |
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| Downloads: | 13 |
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| Metadata: |    |
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| Categories: | Misc.
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