Genetic variation in NDFIP1 modifies the metabolic patterns in immune cells of multiple sclerosis patients.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
01 11 2021
01 11 2021
Historique:
received:
09
06
2021
accepted:
08
10
2021
entrez:
2
11
2021
pubmed:
3
11
2021
medline:
27
1
2022
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 34725369
doi: 10.1038/s41598-021-00528-8
pii: 10.1038/s41598-021-00528-8
pmc: PMC8560952
doi:
Substances chimiques
Carrier Proteins
0
Membrane Proteins
0
NDFIP1 protein, human
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
21371Subventions
Organisme : Promoción de empleo joven y garantía juvenil-CAM
ID : PEJ-3-2019
Organisme : Promoción de empleo joven y garantía juvenil-CAM
ID : PEJD-2019-PRE/SAL-16662
Organisme : Instituto de Salud Carlos III
ID : RETICS-REEM RD16/0015/0013
Informations de copyright
© 2021. The Author(s).
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