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Is Polymorphism in the Apoptosis and Inflammatory Pathway Genes Associated With a Primary Response to Anti-TNF Therapy in Crohn’s Disease Patients?
Anti-tumor necrosis factor (TNF) therapy is used for the induction and maintenance of remission in Crohn’s disease (CD) patients. However, primary nonresponders to initial treatment constitute 20%–40% of cases. The causes of this phenomenon are still unknown. In this study, we aimed to determine the...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7456829/ https://www.ncbi.nlm.nih.gov/pubmed/32922288 http://dx.doi.org/10.3389/fphar.2020.01207 |
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author | Walczak, Michal Lykowska-Szuber, Liliana Plucinska, Marianna Stawczyk-Eder, Kamila Zakerska-Banaszak, Oliwia Eder, Piotr Krela-Kazmierczak, Iwona Michalak, Michal Zywicki, Marek Karlowski, Wojciech M. Szalata, Marlena Dobrowolska, Agnieszka Slomski, Ryszard Skrzypczak-Zielinska, Marzena |
author_facet | Walczak, Michal Lykowska-Szuber, Liliana Plucinska, Marianna Stawczyk-Eder, Kamila Zakerska-Banaszak, Oliwia Eder, Piotr Krela-Kazmierczak, Iwona Michalak, Michal Zywicki, Marek Karlowski, Wojciech M. Szalata, Marlena Dobrowolska, Agnieszka Slomski, Ryszard Skrzypczak-Zielinska, Marzena |
author_sort | Walczak, Michal |
collection | PubMed |
description | Anti-tumor necrosis factor (TNF) therapy is used for the induction and maintenance of remission in Crohn’s disease (CD) patients. However, primary nonresponders to initial treatment constitute 20%–40% of cases. The causes of this phenomenon are still unknown. In this study, we aimed to determine the genetic predictors of the variable reactions of CD patients to anti-TNF therapy. Using long-range PCR libraries and the next-generation sequencing (NGS) method, we performed broad pharmacogenetic studies including a panel of 23 genes (TNFRSF1A, TNFRSF1B, CASP9, FCGR3A, LTA, TNF, FAS, ADAM17, IL17A, IL6, MMP1, MMP3, S100A8, S100A9, S100A12, TLR2, TLR4, TLR9, CD14, IL23R, IL23, IL1R, and IL1B) in a group of 107 diagnosed and clinically characterized CD patients following anti-TNF therapy. In the studied group, we indicated, in total, 598 single nucleotide variants for all analyzed genomic targets. Twelve patients (11.2%) did not respond to the induction therapy, which was associated with alleles in 11 loci located in FCGR3A (rs7539036, rs6672453, rs373184583, and rs12128686), IL1R (rs2041747), TNFRSF1B (rs5746053), IL1B (rs1071676, rs1143639, rs1143637, and rs1143634), and FAS (rs7896789) genes. After multiple comparison corrections, the results were not statistically significant, however for nonresponders the alleles distribution for those loci presented large differences and specified scheme compared to responders and populations. These findings require further investigation in an independent larger cohort before introducing them for a clinical setting, however, we identified an interesting direction. Polymorphism of the FCGR3A, IL1R, TNFRSF1B, IL1B, and FAS genes could be a predictor of the primary response to anti-TNF therapy in CD patients. |
format | Online Article Text |
id | pubmed-7456829 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-74568292020-09-11 Is Polymorphism in the Apoptosis and Inflammatory Pathway Genes Associated With a Primary Response to Anti-TNF Therapy in Crohn’s Disease Patients? Walczak, Michal Lykowska-Szuber, Liliana Plucinska, Marianna Stawczyk-Eder, Kamila Zakerska-Banaszak, Oliwia Eder, Piotr Krela-Kazmierczak, Iwona Michalak, Michal Zywicki, Marek Karlowski, Wojciech M. Szalata, Marlena Dobrowolska, Agnieszka Slomski, Ryszard Skrzypczak-Zielinska, Marzena Front Pharmacol Pharmacology Anti-tumor necrosis factor (TNF) therapy is used for the induction and maintenance of remission in Crohn’s disease (CD) patients. However, primary nonresponders to initial treatment constitute 20%–40% of cases. The causes of this phenomenon are still unknown. In this study, we aimed to determine the genetic predictors of the variable reactions of CD patients to anti-TNF therapy. Using long-range PCR libraries and the next-generation sequencing (NGS) method, we performed broad pharmacogenetic studies including a panel of 23 genes (TNFRSF1A, TNFRSF1B, CASP9, FCGR3A, LTA, TNF, FAS, ADAM17, IL17A, IL6, MMP1, MMP3, S100A8, S100A9, S100A12, TLR2, TLR4, TLR9, CD14, IL23R, IL23, IL1R, and IL1B) in a group of 107 diagnosed and clinically characterized CD patients following anti-TNF therapy. In the studied group, we indicated, in total, 598 single nucleotide variants for all analyzed genomic targets. Twelve patients (11.2%) did not respond to the induction therapy, which was associated with alleles in 11 loci located in FCGR3A (rs7539036, rs6672453, rs373184583, and rs12128686), IL1R (rs2041747), TNFRSF1B (rs5746053), IL1B (rs1071676, rs1143639, rs1143637, and rs1143634), and FAS (rs7896789) genes. After multiple comparison corrections, the results were not statistically significant, however for nonresponders the alleles distribution for those loci presented large differences and specified scheme compared to responders and populations. These findings require further investigation in an independent larger cohort before introducing them for a clinical setting, however, we identified an interesting direction. Polymorphism of the FCGR3A, IL1R, TNFRSF1B, IL1B, and FAS genes could be a predictor of the primary response to anti-TNF therapy in CD patients. Frontiers Media S.A. 2020-08-14 /pmc/articles/PMC7456829/ /pubmed/32922288 http://dx.doi.org/10.3389/fphar.2020.01207 Text en Copyright © 2020 Walczak, Lykowska-Szuber, Plucinska, Stawczyk-Eder, Zakerska-Banaszak, Eder, Krela-Kazmierczak, Michalak, Zywicki, Karlowski, Szalata, Dobrowolska, Slomski and Skrzypczak-Zielinska http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Pharmacology Walczak, Michal Lykowska-Szuber, Liliana Plucinska, Marianna Stawczyk-Eder, Kamila Zakerska-Banaszak, Oliwia Eder, Piotr Krela-Kazmierczak, Iwona Michalak, Michal Zywicki, Marek Karlowski, Wojciech M. Szalata, Marlena Dobrowolska, Agnieszka Slomski, Ryszard Skrzypczak-Zielinska, Marzena Is Polymorphism in the Apoptosis and Inflammatory Pathway Genes Associated With a Primary Response to Anti-TNF Therapy in Crohn’s Disease Patients? |
title | Is Polymorphism in the Apoptosis and Inflammatory Pathway Genes Associated With a Primary Response to Anti-TNF Therapy in Crohn’s Disease Patients? |
title_full | Is Polymorphism in the Apoptosis and Inflammatory Pathway Genes Associated With a Primary Response to Anti-TNF Therapy in Crohn’s Disease Patients? |
title_fullStr | Is Polymorphism in the Apoptosis and Inflammatory Pathway Genes Associated With a Primary Response to Anti-TNF Therapy in Crohn’s Disease Patients? |
title_full_unstemmed | Is Polymorphism in the Apoptosis and Inflammatory Pathway Genes Associated With a Primary Response to Anti-TNF Therapy in Crohn’s Disease Patients? |
title_short | Is Polymorphism in the Apoptosis and Inflammatory Pathway Genes Associated With a Primary Response to Anti-TNF Therapy in Crohn’s Disease Patients? |
title_sort | is polymorphism in the apoptosis and inflammatory pathway genes associated with a primary response to anti-tnf therapy in crohn’s disease patients? |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7456829/ https://www.ncbi.nlm.nih.gov/pubmed/32922288 http://dx.doi.org/10.3389/fphar.2020.01207 |
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