Genetic variation in NDFIP1 modifies the metabolic patterns in immune cells of multiple sclerosis patients

Abstract 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...

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Autores principales:	Pilar López-Cotarelo, Adela González-Jiménez, Teresa Agudo-Jiménez, Judith Abarca-Zabalía, Yolanda Aladro, Belén Pilo, Manuel Comabella, Laura Espino-Paisán, Elena Urcelay
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3f10b6410d8943f38744881654a3e221
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spelling	oai:doaj.org-article:3f10b6410d8943f38744881654a3e2212021-11-08T10:54:17ZGenetic variation in NDFIP1 modifies the metabolic patterns in immune cells of multiple sclerosis patients10.1038/s41598-021-00528-82045-2322https://doaj.org/article/3f10b6410d8943f38744881654a3e2212021-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-00528-8https://doaj.org/toc/2045-2322Abstract 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.Pilar López-CotareloAdela González-JiménezTeresa Agudo-JiménezJudith Abarca-ZabalíaYolanda AladroBelén PiloManuel ComabellaLaura Espino-PaisánElena UrcelayNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Pilar López-Cotarelo Adela González-Jiménez Teresa Agudo-Jiménez Judith Abarca-Zabalía Yolanda Aladro Belén Pilo Manuel Comabella Laura Espino-Paisán Elena Urcelay Genetic variation in NDFIP1 modifies the metabolic patterns in immune cells of multiple sclerosis patients
description	Abstract 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	article
author	Pilar López-Cotarelo Adela González-Jiménez Teresa Agudo-Jiménez Judith Abarca-Zabalía Yolanda Aladro Belén Pilo Manuel Comabella Laura Espino-Paisán Elena Urcelay
author_facet	Pilar López-Cotarelo Adela González-Jiménez Teresa Agudo-Jiménez Judith Abarca-Zabalía Yolanda Aladro Belén Pilo Manuel Comabella Laura Espino-Paisán Elena Urcelay
author_sort	Pilar López-Cotarelo
title	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_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_sort	genetic variation in ndfip1 modifies the metabolic patterns in immune cells of multiple sclerosis patients
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/3f10b6410d8943f38744881654a3e221
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Genetic variation in NDFIP1 modifies the metabolic patterns in immune cells of multiple sclerosis patients

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