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Background: GG homozygosity for the risk gene variant rs7665090 has been reported to enhance nuclear factor kappa B (NFκB) activity in T cells from multiple sclerosis (MS) patients. Here, we investigated the association between this polymorphism and the response to different disease-modifying therapies in MS.
Methods: The rs7665090 polymorphism was genotyped in 558 MS patients treated with injectable therapies [IFNβ (n = 213) and glatiramer acetate (n = 55)], oral therapies [dimethylfumarate (n = 97), teriflunomide (n = 41), and fingolimod (n = 37)], and natalizumab (n = 115). Treatment response was assessed after 1 year for injectable therapies using the Rio Score, which considers relapses, EDSS progression, and radiological activity on MRI. For oral therapies and natalizumab, response was evaluated after 2 years based on clinical and radiological disease activity. Univariable and multivariable logistic regression analyses were performed to assess treatment response for each therapy independently.
Results: GG homozygosity was associated with a favorable response outcome in patients treated with IFNβ in the multivariable analysis after adjusting for age and EDSS at treatment onset [OR 0.42 (0.18-0.94); p = 0.037]. This finding was restricted to MS patients carrying the GG risk genotype and seemed specific for IFNβ treatment, since the rs7665090 polymorphism did not influence the response to the other MS therapies.
Conclusion: The polymorphism rs7665090 is associated with a favorable response to IFNβ. This study illustrates how genotyping this polymorphism could serve as a useful biomarker in clinical practice to help identify MS patients who are likely to respond favorably to treatment, and encourages further replication in larger cohorts.
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http://dx.doi.org/10.1111/ene.70227 | DOI Listing |
Eur J Neurol
July 2025
Servei de Neurologia, Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Institut de Recerca Vall d'Hebron (VHIR), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain.
Background: GG homozygosity for the risk gene variant rs7665090 has been reported to enhance nuclear factor kappa B (NFκB) activity in T cells from multiple sclerosis (MS) patients. Here, we investigated the association between this polymorphism and the response to different disease-modifying therapies in MS.
Methods: The rs7665090 polymorphism was genotyped in 558 MS patients treated with injectable therapies [IFNβ (n = 213) and glatiramer acetate (n = 55)], oral therapies [dimethylfumarate (n = 97), teriflunomide (n = 41), and fingolimod (n = 37)], and natalizumab (n = 115).
Mult Scler Relat Disord
February 2024
UCSF Weill Institute for Neurosciences, University of California San Francisco, San Francisco, CA, USA.
Background: Our previous study identified a significant association between lower time spent outdoors, as a proxy of sun exposure, and a higher risk of pediatric-onset multiple sclerosis (POMS). UV radiation modulates the expression of several genes, but it is unknown whether these genes modify the effect of sun exposure on POMS risk.
Methods: In an age- and sex-matched case-control study, we evaluated the additive and multiplicative interactions between time spent outdoors and genetic non-HLA risk variants for developing POMS within the metabolic pathways of UV radiation, including CD28(rs6435203), CD86(rs9282641), and NFkB1(rs7665090) and the top two HLA risk factors (presence of DRB1×15 and absence of A*02).
J Neurol Neurosurg Psychiatry
July 2023
UCSF Weill Institute for Neurosciences, University of California San Francisco, San Francisco, California, USA
Background: We previously reported an association between household chemical exposures and an increased risk of paediatric-onset multiple sclerosis.
Methods: Using a case-control paediatric multiple sclerosis study, gene-environment interaction between exposure to household chemicals and genotypes for risk of paediatric-onset multiple sclerosis was estimated.Genetic risk factors of interest included the two major HLA multiple sclerosis risk factors, the presence of and the absence of and multiple sclerosis risk variants within the metabolic pathways of common household toxic chemicals, including (rs2069852), (rs2187163) and (rs7665090).
Int J Mol Sci
July 2022
Laboratorio de Genética de Enfermedades Complejas, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), 28040 Madrid, Spain.
Nat Commun
December 2018
Department of Neurology, Yale School of Medicine, New Haven, CT, 06511, USA.