Genetic variation in NDFIP1 modifies the metabolic patterns in immune cells of multiple sclerosis patients
López-Cotarelo, Pilar (Instituto de Investigación Sanitaria del Hospital Clínico San Carlos)
González-Jiménez, Adela (Instituto de Investigación Sanitaria del Hospital Clínico San Carlos)
Agudo-Jiménez, Teresa (Instituto de Investigación Sanitaria del Hospital Clínico San Carlos)
Abarca-Zabalía, Judith (Instituto de Investigación Sanitaria del Hospital Clínico San Carlos)
Aladro, Yolanda (Hospital Universitario de Getafe (Madrid))
Pilo, Belén (Hospital Universitario de Getafe (Madrid))
Comabella López, Manuel (Vall d'Hebron Institut de Recerca (VHIR))
Espino-Paisan, Laura (Instituto de Investigación Sanitaria del Hospital Clínico San Carlos)
Urcelay, Elena (Instituto de Investigación Sanitaria del Hospital Clínico San Carlos)

Data:	2021
Resum:	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.
Ajuts:	Ministerio de Economía y Competitividad PI16/01259 Instituto de Salud Carlos III PI20/01634
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Genetic markers ; Immunogenetics ; Autoimmunity ; Gene regulation in immune cells ; Neurological disorders ; Multiple sclerosis
Publicat a:	Scientific reports, Vol. 11 (november 2021) , ISSN 2045-2322

DOI: 10.1038/s41598-021-00528-8
PMID: 34725369

9 p, 1.7 MB

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