The Variant rs7665090 Is Associated With Interferon-Beta Response in Multiple Sclerosis Patients

Area of Science:

• Neuroimmunology
• Pharmacogenetics
• Multiple Sclerosis Therapeutics

Background:

• The GG genotype of the rs7665090 risk variant in multiple sclerosis (MS) patients is associated with enhanced nuclear factor kappa B (NFκB) activity in T cells.
• Understanding the impact of genetic polymorphisms on treatment response is crucial for optimizing MS management.

Purpose of the Study:

• To investigate the association between the rs7665090 polymorphism and treatment response to various disease-modifying therapies (DMTs) in multiple sclerosis (MS) patients.
• To determine if rs7665090 genotype can predict therapeutic efficacy in MS.

Main Methods:

• Genotyping of the rs7665090 polymorphism in 558 MS patients treated with different DMTs, including injectable (IFNβ, glatiramer acetate), oral (dimethylfumarate, teriflunomide, fingolimod), and natalizumab.
• Treatment response was assessed after 1-2 years using clinical and radiological outcomes (Rio Score, EDSS, MRI).
• Statistical analyses, including univariable and multivariable logistic regression, were employed to evaluate treatment response based on genotype.

Main Results:

• GG homozygosity for rs7665090 was significantly associated with a favorable treatment response in MS patients receiving interferon-beta (IFNβ) therapy (OR 0.42; p=0.037).
• This association was specific to IFNβ treatment and did not extend to other DMTs evaluated in the study.
• The rs7665090 polymorphism appears to be a predictive biomarker for IFNβ response in a subset of MS patients.

Conclusions:

• The rs7665090 polymorphism serves as a predictive biomarker for favorable response to interferon-beta (IFNβ) treatment in multiple sclerosis (MS).
• Genotyping rs7665090 could aid clinicians in identifying MS patients most likely to benefit from IFNβ therapy.
• Further validation in larger patient cohorts is recommended to confirm these findings and their clinical utility.