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Genetic variation in NDFIP1 modifies the metabolic patterns in immune cells of multiple sclerosis patients
One of the 233 polymorphisms associated with multiple sclerosis (MS) susceptibility lies within the NDFIP1 gene, and it was previously identified as eQTL in healthy controls. NDFIP1 shows interesting immune functions and is involved in the development of the central nervous system. We aimed at study...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8560952/ https://www.ncbi.nlm.nih.gov/pubmed/34725369 http://dx.doi.org/10.1038/s41598-021-00528-8 |
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author | López-Cotarelo, Pilar González-Jiménez, Adela Agudo-Jiménez, Teresa Abarca-Zabalía, Judith Aladro, Yolanda Pilo, Belén Comabella, Manuel Espino-Paisán, Laura Urcelay, Elena |
author_facet | López-Cotarelo, Pilar González-Jiménez, Adela Agudo-Jiménez, Teresa Abarca-Zabalía, Judith Aladro, Yolanda Pilo, Belén Comabella, Manuel Espino-Paisán, Laura Urcelay, Elena |
author_sort | López-Cotarelo, Pilar |
collection | PubMed |
description | One of the 233 polymorphisms associated with multiple sclerosis (MS) susceptibility lies within the NDFIP1 gene, and it was previously identified as eQTL in healthy controls. NDFIP1 shows interesting immune functions and is involved in the development of the central nervous system. We aimed at studying the NDFIP1 variant on activation and metabolism of immune cells. NDFIP1 mRNA and protein expression were assessed in PBMCs by qPCR and western blot in 87 MS patients and 84 healthy controls genotyped for rs4912622. Immune activation after PHA stimulation was evaluated by CD69 upregulation, and metabolic function of both basal and PHA-activated lymphocytes was studied by Seahorse Xfp-Analyzer. In minor-allele homozygous controls but not in patients, we found higher NDFIP1 expression, significantly reduced protein levels, and CD69 upregulation in B- and T-cells. PBMCs from minor-allele homozygous controls showed significantly higher basal mitochondrial respiration and ATP production compared to major-allele carriers, while minor-allele homozygous patients showed significantly lower metabolic activity than carriers of the major allele. In conclusion, we describe associations in minor-allele homozygous controls with lower levels of NDFIP1 protein, CD69 upregulation, and raised mitochondrial activity, which are not replicated in MS patients, suggesting a NDFIP1 differential effect in health and disease. |
format | Online Article Text |
id | pubmed-8560952 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-85609522021-11-03 Genetic variation in NDFIP1 modifies the metabolic patterns in immune cells of multiple sclerosis patients López-Cotarelo, Pilar González-Jiménez, Adela Agudo-Jiménez, Teresa Abarca-Zabalía, Judith Aladro, Yolanda Pilo, Belén Comabella, Manuel Espino-Paisán, Laura Urcelay, Elena Sci Rep Article One of the 233 polymorphisms associated with multiple sclerosis (MS) susceptibility lies within the NDFIP1 gene, and it was previously identified as eQTL in healthy controls. NDFIP1 shows interesting immune functions and is involved in the development of the central nervous system. We aimed at studying the NDFIP1 variant on activation and metabolism of immune cells. NDFIP1 mRNA and protein expression were assessed in PBMCs by qPCR and western blot in 87 MS patients and 84 healthy controls genotyped for rs4912622. Immune activation after PHA stimulation was evaluated by CD69 upregulation, and metabolic function of both basal and PHA-activated lymphocytes was studied by Seahorse Xfp-Analyzer. In minor-allele homozygous controls but not in patients, we found higher NDFIP1 expression, significantly reduced protein levels, and CD69 upregulation in B- and T-cells. PBMCs from minor-allele homozygous controls showed significantly higher basal mitochondrial respiration and ATP production compared to major-allele carriers, while minor-allele homozygous patients showed significantly lower metabolic activity than carriers of the major allele. In conclusion, we describe associations in minor-allele homozygous controls with lower levels of NDFIP1 protein, CD69 upregulation, and raised mitochondrial activity, which are not replicated in MS patients, suggesting a NDFIP1 differential effect in health and disease. Nature Publishing Group UK 2021-11-01 /pmc/articles/PMC8560952/ /pubmed/34725369 http://dx.doi.org/10.1038/s41598-021-00528-8 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article López-Cotarelo, Pilar González-Jiménez, Adela Agudo-Jiménez, Teresa Abarca-Zabalía, Judith Aladro, Yolanda Pilo, Belén Comabella, Manuel Espino-Paisán, Laura Urcelay, Elena Genetic variation in NDFIP1 modifies the metabolic patterns in immune cells of multiple sclerosis patients |
title | Genetic variation in NDFIP1 modifies the metabolic patterns in immune cells of multiple sclerosis patients |
title_full | Genetic variation in NDFIP1 modifies the metabolic patterns in immune cells of multiple sclerosis patients |
title_fullStr | Genetic variation in NDFIP1 modifies the metabolic patterns in immune cells of multiple sclerosis patients |
title_full_unstemmed | Genetic variation in NDFIP1 modifies the metabolic patterns in immune cells of multiple sclerosis patients |
title_short | Genetic variation in NDFIP1 modifies the metabolic patterns in immune cells of multiple sclerosis patients |
title_sort | genetic variation in ndfip1 modifies the metabolic patterns in immune cells of multiple sclerosis patients |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8560952/ https://www.ncbi.nlm.nih.gov/pubmed/34725369 http://dx.doi.org/10.1038/s41598-021-00528-8 |
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