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Article Abstract

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://www.ncbi.nlm.nih.gov/pmc/articles/PMC12263501PMC
http://dx.doi.org/10.1111/ene.70227DOI Listing

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Article Synopsis
  • Deficiencies in the enzyme Mannosidase β (MANBA) are linked to neurological issues and infections, with a specific genetic polymorphism (rs7665090) associated with an increased risk of multiple sclerosis (MS).
  • A study analyzed lymphocytes from 152 MS patients and 112 healthy controls, revealing that MS patients displayed significantly lower MANBA mRNA expression and enzymatic activity compared to controls.
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  • The study explores how a specific genetic risk variant (rs7665090) near the NFKB1 gene affects astrocytes, a type of central nervous system (CNS) cell, in relation to multiple sclerosis (MS).
  • The researchers found that this risk variant increases NF-κB signaling and gene expression in astrocytes, which leads to increased recruitment of immune cells (lymphocytes) into the CNS and larger lesions in MS.
  • Ultimately, the research suggests that genetic factors may lead to dysfunctional astrocyte behavior, allowing more immune cells to access the CNS, and contributing to autoimmune inflammation seen in MS.
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