Genetic factors implicated in the response to fingolimod treatment in multiple sclerosis patients: results from a pharmacogenetic meta-analysis

Background: Environmental and genetic factors are thought to be involved in the pathogenesis of multiple sclerosis (MS). Polymorphisms of tumor necrosis factor (TNF)-α −308 were implicated in MS risk in several case–control association studies. However, the studies have shown inconsistent results. Objectives: To address the association of G/A polymorphisms of TNF-α −308 with MS risk by meta-analysis. Methods: Thirteen studies were included. Pooled odds ratios (ORs) together with 95% confidence intervals (CIs) were calculated. Results: A total of 1870 cases and 2769 controls were included in the meta-analysis. The pooled result indicated that −308 A allele is significantly associated with reduced risk of MS compared with −308 G allele (A vs. G, p = 0.022). The same pattern of the result was also obtained in the contrasts of AA + GA vs. GG ( p = 0.008) and GA vs. GG ( p = 0.007). For AA vs. GG or AA vs. GA + GG, no significant association was detected most likely caused by very low frequency or non-availability of homozygote genotype AA for all of the studies. Conclusions: TNF-α −308 A allele is associated with reduced risk of MS.

Download Full-text

Interferon-beta injection in multiple sclerosis patients is related to the induction of headache and flu-like pain symptoms: a systematic review and meta-analysis of randomised controlled trials

Current Neuropharmacology ◽

10.2174/1570159x19666211101142115 ◽

2021 ◽

Vol 19 ◽

Author(s):

Leonardo Gomes Pereira ◽

Gabriela Trevisan ◽

Patrícia Rodrigues ◽

Fernanda Tibolla Viero ◽

Julia Maria Frare ◽

...

Keyword(s):

Multiple Sclerosis ◽

Systematic Review ◽

Adverse Effects ◽

Randomised Controlled Trials ◽

Meta Analysis ◽

Controlled Trials ◽

First Choice ◽

Pain Symptoms ◽

Randomised Controlled ◽

Multiple Sclerosis Patients

: Multiple sclerosis (MS) is a chronic neurodegenerative, inflammatory and autoimmune disease characterised by the demyelination of the central nervous system. One of the main approaches to treating MS is the use of disease-modifying therapies (DMTs). Among the DMTs are interferons (IFNs), which are cytokines responsible for controlling the activity of the immune system, exerting immunomodulatory, antiviral, and antiproliferative activities. IFN-beta (IFN-β) is the first-choice drug used to treat relapsing-remitting MS. However, the administration of IFN-β causes numerous painful adverse effects, resulting in lower adherence to the treatment. Therefore, this study aimed to investigate the headache and flu-like pain symptoms observed after IFNβ injection in MS patients using a systematic review and meta-analysis of randomised controlled trials. The search of research databases identified 2370 articles. Nine articles were included (three involving IFNβ-1b and six involving IFNβ-1a). All studies included in the meta-analysis had a low risk of bias. Headache and flu-like pain symptoms frequency increased in MS patients treated with IFN-β. Thus, the adverse effects of headache and flu-like pain symptoms appear to be linked to IFN-β treatment in MS. The protocol of the study was registered in the Prospective International Registry of Systematic Reviews.

Download Full-text

NLRP3 polymorphisms and response to interferon-beta in multiple sclerosis patients

Multiple Sclerosis Journal ◽

10.1177/1352458517739137 ◽

2017 ◽

Vol 24 (11) ◽

pp. 1507-1510 ◽

Cited By ~ 4

Author(s):

Sunny Malhotra ◽

Melissa Sorosina ◽

Jordi Río ◽

Silvia Peroni ◽

Luciana Midaglia ◽

...

Keyword(s):

Multiple Sclerosis ◽

Interferon Beta ◽

Meta Analysis ◽

Nlrp3 Gene ◽

Radiological Criteria ◽

Pyrin Domain ◽

Relapsing Remitting ◽

Multiple Sclerosis Patients

We aimed to investigate whether NLR family, pyrin domain containing 3 (NLRP3) polymorphisms are associated with the response to interferon-beta (IFNβ) in multiple sclerosis (MS) patients. A total of 14 NLRP3 polymorphisms were genotyped in a cohort of 665 relapsing-remitting MS patients recruited across 5 centers and classified into responders and non-responders according to clinical-radiological criteria after 1 year of IFNβ treatment. A meta-analysis failed to demonstrate significant associations between the response to IFNβ and NLRP3 polymorphisms. These findings do not support a role of polymorphisms located in the NLRP3 gene and the response to IFNβ in MS patients.

Download Full-text

Modifying effects of HLA-DRB1 allele interactions on age at onset of multiple sclerosis in Western Australia

Multiple Sclerosis Journal ◽

10.1177/1352458509350312 ◽

2009 ◽

Vol 16 (1) ◽

pp. 15-20 ◽

Cited By ~ 14

Author(s):

Jing-Shan Wu ◽

Wei Qiu ◽

Alison Castley ◽

Ian James ◽

Frank L Mastaglia ◽

...

Keyword(s):

Multiple Sclerosis ◽

High Resolution ◽

Genetic Factors ◽

Risk Allele ◽

Age At Onset ◽

Demyelinating Diseases ◽

Epistatic Interactions ◽

Drb1 Locus ◽

Disease Modifying ◽

Multiple Sclerosis Patients

The contribution of genetic factors to the age at onset in multiple sclerosis is poorly understood. Our objective was to investigate the disease modifying effects of HLA-DRB1 alleles and allele interactions on age at onset of multiple sclerosis. High-resolution four-digit HLA-DRB1 genotyping was performed in a cohort of 461 multiple sclerosis patients from the Perth Demyelinating Diseases Database. Carriage of the HLA-DRB1*1501 risk allele was not significantly associated with age at onset but HLA-DRB1*0801 was associated with a later onset of the disease. The HLA-DRB1*0401 allele was associated with a reduced age at onset when combined with DRB1*1501 but may delay age at onset when combined with DRB1*0801. These findings indicate that epistatic interactions at the HLA-DRB1 locus have significant modifying effects on age at onset of multiple sclerosis and demonstrate the value of high-resolution genotyping in detecting such associations.

Download Full-text

Effect of Exercise on Fatigue in Multiple Sclerosis Patients: A Network Meta-analysis

International Journal of Sports Medicine ◽

10.1055/a-1524-1935 ◽

2021 ◽

Author(s):

Yuting Chen ◽

Shanshan Xu ◽

Jiran Shen ◽

Hui Yang ◽

Wei Xu ◽

...

Keyword(s):

Multiple Sclerosis ◽

Web Of Science ◽

Meta Analysis ◽

Cochrane Library ◽

Control Group ◽

Inclusion Criteria ◽

Randomized Controlled ◽

Different Types ◽

Multiple Sclerosis Patients ◽

Better Than

AbstractFew studies have directly compared the effects of different exercise therapies on reducing fatigue in patients with multiple sclerosis. Thus, we conducted a Frequentist network meta-analysis to analyze and compare the effectiveness of different types of exercise on reducing multiple sclerosis-related fatigue. Relevant randomized controlled trials were searched in PubMed, Web of Science and Cochrane Library databases from the date of their inception up to April 1, 2021. In total, 27 articles involving 1470 participants and 10 types of interventions met the inclusion criteria. The results indicated that aquatic exercise ranked as the most effective among these interventions, and aerobic exercise had small-to-moderate effect sizes. Most of the interventions were shown to be better than the control group, except for climbing. Climbing was the only intervention that ranked worse than the controls. All of these findings merit further investigation in future clinical trials.

Download Full-text