scholarly journals The Effects of The MTHFR 677C>T (Rs1801133) Genetic Variant on Susceptibility and Disability in Multiple Sclerosis Patients are Mediated by Homocysteine But Not Folate Levels

2021 ◽  
Author(s):  
Claudia Mara Ribeiro ◽  
Sayonara Rangel Oliveira ◽  
Tamires Flauzino ◽  
Daniela Frizon Alfieri ◽  
Andrea Name Colado Simão ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Vitamin D3 ◽  
Activity Index ◽  
Inflammatory Biomarkers ◽  
Disability Progression ◽  
Reactive Protein ◽  
Disability Status ◽  
Male Sex ◽  
Polymerase Chain ◽  
Multiple Sclerosis Patients

Abstract We investigated whether the MTHFR 677C>T (rs1801133) variant and plasma homocysteine and folate are associated with multiple sclerosis (MS), disability, disability progression, and inflammatory biomarkers. We included 163 MS patients categorized using the Expanded Disability Status Scale (EDSS) as mild (EDSS<3) and moderate/high (EDSS≥3) disability, and 226 healthy controls. Disability progression was evaluated using Multiple Sclerosis Severity Score (MSSS) and the MTHFR 677C>T was genotyped using real time polymerase chain reaction. The levels of some inflammatory biomarkers and inflammatory activity index (IAI) were determined. There was no association between the MTHFR 677 C>T genotypes and MS, EDSS, and MSSS (p>0.05). Plasma folate and homocysteine were higher and adiponectin was lower in MS patients than controls (p<0.001). Moreover, 21.8% of the EDSS variance was explained by age, IAI and C-reactive protein (CRP) (all positively associated); 10.9% of the MSSS variance was predicted by IAI and CRP (both positively) and vitamin D3 (negatively), whereas 54.4% of the MS-EDSS-MSSS score was explained by the regression on age, IAI, homocysteine, folate, and CRP (all positively) and adiponectin, body mass index, and vitamin D3 (all negatively), female sex and the MTHFR 677 TT genotype. In patients and controls, 16.6% of the variance in the homocysteine was explained by the MTHFR 677 TT genotype and age (both positively), folate (negatively) and male sex. In conclusion, the MTHFR 677C>T variant was not directly associated with MS, disability, and disability progression; however, the TT genotype showed indirect effects on MS susceptibility and disability mediated by homocysteine.

scholarly journals The Effects of the MTHFR 677C>T (rs1801133) Genetic Variant on Susceptibility and Disability in Multiple Sclerosis Patients are Mediated by Homocysteine but Not Folate Levels

2021 ◽  
Author(s):  
Claudia Mara Ribeiro ◽  
Sayonara Rangel Oliveira ◽  
Tamires Flauzino ◽  
Daniela Frizon Alfieri ◽  
Andrea Name Colado Simão ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Vitamin D3 ◽  
Activity Index ◽  
Inflammatory Biomarkers ◽  
Disability Progression ◽  
Reactive Protein ◽  
Disability Status ◽  
Male Sex ◽  
Polymerase Chain ◽  
Multiple Sclerosis Patients

Abstract We investigated whether the MTHFR 677C>T (rs1801133) variant and plasma homocysteine and folate are associated with multiple sclerosis (MS), disability, disability progression, and inflammatory biomarkers. We included 163 MS patients categorized using the Expanded Disability Status Scale (EDSS) as mild (EDSS<3) and moderate/high (EDSS≥3) disability, and 226 healthy controls. Disability progression was evaluated using Multiple Sclerosis Severity Score (MSSS) and the MTHFR 677C>T was genotyped using real time polymerase chain reaction. The levels of some inflammatory biomarkers and inflammatory activity index (IAI) were determined. There was no association between the MTHFR 677 C>T genotypes and MS, EDSS, and MSSS (p>0.05). Plasma folate and homocysteine were higher and adiponectin was lower in MS patients than controls (p<0.001). Moreover, 21.8% of the EDSS variance was explained by age, IAI and C-reactive protein (CRP) (all positively associated); 10.9% of the MSSS variance was predicted by IAI and CRP (both positively) and vitamin D3 (negatively), whereas 54.4% of the MS-EDSS-MSSS score was explained by the regression on age, IAI, homocysteine, folate, and CRP (all positively) and adiponectin, body mass index, and vitamin D3 (all negatively), female sex and the MTHFR 677 TT genotype. In patients and controls, 16.6% of the variance in the homocysteine was explained by the MTHFR 677 TT genotype and age (both positively), folate (negatively) and male sex. In conclusion, the MTHFR 677C>T variant was not directly associated with MS, disability, and disability progression; however, the TT genotype showed indirect effects on MS susceptibility and disability mediated by homocysteine.

scholarly journals The Effects of the MTHFR 677C>T (rs1801133) Genetic Variant on Susceptibility and Disability in Multiple Sclerosis Patients are Mediated by Homocysteine but not Folate Levels

2021 ◽  
Author(s):  
Claudia Mara Ribeiro ◽  
Sayonara Rangel Oliveira ◽  
Tamires Flauzino ◽  
Daniela Frizon Alfieri ◽  
Andrea Name Colado Simão ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Vitamin D3 ◽  
Activity Index ◽  
Inflammatory Biomarkers ◽  
Disability Progression ◽  
Reactive Protein ◽  
Disability Status ◽  
Male Sex ◽  
Polymerase Chain ◽  
Multiple Sclerosis Patients

Abstract We investigated whether the MTHFR 677C>T (rs1801133) variant and plasma homocysteine and folate are associated with multiple sclerosis (MS), disability, disability progression, and inflammatory biomarkers. We included 163 MS patients categorized using the Expanded Disability Status Scale (EDSS) as mild (EDSS<3) and moderate/high (EDSS≥3) disability, and 226 healthy controls. Disability progression was evaluated using Multiple Sclerosis Severity Score (MSSS) and the MTHFR 677C>T was genotyped using real time polymerase chain reaction. The levels of some inflammatory biomarkers and inflammatory activity index (IAI) were determined. There was no association between the MTHFR 677 C>T genotypes and MS, EDSS, and MSSS (p>0.05). Plasma folate and homocysteine were higher and adiponectin was lower in MS patients than controls (p<0.001). Moreover, 21.8% of the EDSS variance was explained by age, IAI and C-reactive protein (CRP) (all positively associated); 10.9% of the MSSS variance was predicted by IAI and CRP (both positively) and vitamin D3 (negatively), whereas 54.4% of the MS-EDSS-MSSS score was explained by the regression on age, IAI, homocysteine, folate, and CRP (all positively) and adiponectin, body mass index, and vitamin D3 (all negatively), female sex and the MTHFR 677 TT genotype. In patients and controls, 16.6% of the variance in the homocysteine was explained by the MTHFR 677 TT genotype and age (both positively), folate (negatively) and male sex. In conclusion, the MTHFR 677C>T variant was not directly associated with MS, disability, and disability progression; however, the TT genotype showed indirect effects on MS susceptibility and disability mediated by homocysteine.

scholarly journals Determinants of therapeutic lag in multiple sclerosis

2021 ◽  
pp. 135245852098130
Author(s):  
Izanne Roos ◽  
Emmanuelle Leray ◽  
Federico Frascoli ◽  
Romain Casey ◽  
J William L Brown ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Expanded Disability Status Scale ◽  
Disability Progression ◽  
Delayed Onset ◽  
Disease Characteristics ◽  
Disability Status ◽  
Male Sex ◽  
Pre Treatment ◽  
Patient Subgroups

Background: A delayed onset of treatment effect, termed therapeutic lag, may influence the assessment of treatment response in some patient subgroups. Objectives: The objective of this study is to explore the associations of patient and disease characteristics with therapeutic lag on relapses and disability accumulation. Methods: Data from MSBase, a multinational multiple sclerosis (MS) registry, and OFSEP, the French MS registry, were used. Patients diagnosed with MS, minimum 1 year of exposure to MS treatment and 3 years of pre-treatment follow-up, were included in the analysis. Studied outcomes were incidence of relapses and disability accumulation. Therapeutic lag was calculated using an objective, validated method in subgroups stratified by patient and disease characteristics. Therapeutic lag under specific circumstances was then estimated in subgroups defined by combinations of clinical and demographic determinants. Results: High baseline disability scores, annualised relapse rate (ARR) ⩾ 1 and male sex were associated with longer therapeutic lag on disability progression in sufficiently populated groups: females with expanded disability status scale (EDSS) < 6 and ARR < 1 had mean lag of 26.6 weeks (95% CI = 18.2–34.9), males with EDSS < 6 and ARR < 1 31.0 weeks (95% CI = 25.3–36.8), females with EDSS < 6 and ARR ⩾ 1 44.8 weeks (95% CI = 24.5–65.1), and females with EDSS ⩾ 6 and ARR < 1 54.3 weeks (95% CI = 47.2–61.5). Conclusions: Pre-treatment EDSS and ARR are the most important determinants of therapeutic lag.

scholarly journals Polymorphisms in the CIITA −168A/G (rs3087456) and CIITA +1614G/C (rs4774) may influence severity in multiple sclerosis patients

2019 ◽  
Vol 77 (3) ◽  
pp. 166-173 ◽  
Author(s):  
Valéria Coelho Santa Rita Pereira ◽  
Fabrícia Lima Fontes-Dantas ◽  
Eduardo Ribeiro Paradela ◽  
Fabíola Rachid Malfetano ◽  
Simone de Souza Batista Scherpenhuijzen ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Course ◽  
Nucleotide Polymorphisms ◽  
Expanded Disability Status Scale ◽  
Disability Progression ◽  
Single Nucleotide ◽  
Disability Status ◽  
Multiple Sclerosis Patients ◽  
The Impact ◽  
Lower Odds Ratio

ABSTRACT It is currently unknown how genetic factors may influence the clinical course of multiple sclerosis (MS). Objective: We examined the impact of CIITA polymorphisms −168A/G (rs3087456) and +1614G/C (rs4774) on the risk of disability progression, severity and on responses to first-line immunomodulator treatments. Methods: Genomic DNA was extracted from blood samples. We used ABI3730xl and GeneMapper v.4.0 software to identify genotype variations. All patients were followed up and clinically reassessed at three-month intervals. Disability progression was measured by the Expanded Disability Status Scale and disease severity by the Multiple Sclerosis Spasticity Scale (MSSS). Results: We included 37 men and 80 women. We found no evidence regarding the influence of the single nucleotide polymorphisms studied in the Expanded Disability Status Scale or therapeutic response of the evaluated drugs. We performed a logistic regression analysis with the MSSS and found that a less severe MS course was associated with wild type CIITA −168AA and CIITA +1614GG, as the chance of the patient progressing to MSSS2 and MSSS3 decreased in 61% and 75% with CIITA −168AA and 66% and 75% with CIITA +1614GG, respectively (p < 0.0001). Although less significant, the CIITA +1614 GC also pointed to a less severe MS course and the chance of the patient progressing to MSSS3 decreased 79% (p = 0.015). We also observed that the CIITA −168GG genotype was more frequent in MSSS2 and MSSS3 and had 40% lower odds ratio to becoming more severe MS. Conclusion: These data suggest that CIITA −168AA, CIITA +1614GG and CIITA +1614 GC polymorphisms may be associated with a better MS clinical course. This knowledge may be useful for a better understanding of MS and its therapeutic management.

Assessment of biochemical determinants in Multiple Sclerosis patients following the oral administration of β-D-Mannuronic acid [M2000]

2020 ◽  
Vol 17 ◽  
Author(s):  
Mohamad Reza Nikouei Moghaddam ◽  
Monireh Movahedi ◽  
Maryam Bananej ◽  
Soheil Najafi ◽  
Nahid Beladi Moghadam ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Uric Acid ◽  
Vitamin D3 ◽  
Chronic Inflammatory Disease ◽  
Toxic Effects ◽  
Control Group ◽  
Therapeutic Effects ◽  
Mannuronic Acid ◽  
Anti Inflammatory ◽  
Multiple Sclerosis Patients

Background: Multiple sclerosis is an autoimmune chronic inflammatory disease of the central nervous system that can lead to some serious disabilities. Despite using various immunomodulatory and anti-inflammatory drugs that have therapeutic effects, they cannot reduce its progression completely, and have some unwanted side effects too. The immunomodulatory and anti-inflammatory effects of the β-D-Mannuronic acid [M2000] have been proven in several surveys, and the present research was designed to determine its toxicity and therapeutic effects in MS patients. Methods: This study was performed on 15 MS patients who took 25 mg/kg/day the oral form of the β-D-Mannuronic acid for six months, and 15 healthy people as a control group. Serum levels of Urea, Creatinine, GGT, Vitamin D3, Uric acid, and Anti-Phospholipids were compared to evaluate the therapeutic and possible toxic effects of this drug after this period. Results: Non- toxic effects through the study of Urea, Creatinine, GGT, and non-significant changes in Uric acid and AntiPhospholipids levels, besides a significant rise in Vitamin, D3 levels in the M2000 treated cases were found. Conclusions: Our results suggested that β-D-Mannuronic acid is a safe drug and has no toxicity when administered orally and also has some therapeutic effects in MS patients.

scholarly journals Assessment of Disability Progression Independent of Relapse and Brain MRI Activity in Patients with Multiple Sclerosis in Poland

2021 ◽  
Vol 10 (4) ◽  
pp. 868
Author(s):  
Katarzyna Kapica-Topczewska ◽  
François Collin ◽  
Joanna Tarasiuk ◽  
Agata Czarnowska ◽  
Monika Chorąży ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Brain Activity ◽  
Brain Mri ◽  
Disability Progression ◽  
Program Monitoring ◽  
Therapeutic Program ◽  
Relapsing Remitting ◽  
Second Year ◽  
Multiple Sclerosis Patients ◽  
Relapsing Remitting Multiple Sclerosis

The aim of the study was to verify the association of clinical relapses and brain activity with disability progression in relapsing/remitting multiple sclerosis patients receiving disease-modifying treatments in Poland. Disability progression was defined as relapse-associated worsening (RAW), progression independent of relapse activity (PIRA), and progression independent of relapses and brain MRI Activity (PIRMA). Data from the Therapeutic Program Monitoring System were analyzed. Three panels of patients were identified: R0, no relapse during treatment, and R1 and R2 with the occurrence of relapse during the first and the second year of treatment, respectively. In the R0 panel, we detected 4.6% PIRA patients at 24 months (p < 0.001, 5.0% at 36 months, 5.6% at 48 months, 6.1% at 60 months). When restricting this panel to patients without brain MRI activity, we detected 3.0% PIRMA patients at 12 months, 4.5% at 24 months, and varying from 5.3% to 6.2% between 36 and 60 months of treatment, respectively. In the R1 panel, RAW was detected in 15.6% patients at 12 months and, in the absence of further relapses, 9.7% at 24 months and 6.8% at 36 months of treatment. The R2 group was associated with RAW significantly more frequently at 24 months compared to the R1 at 12 months (20.7%; p < 0.05), but without a statistical difference later on. In our work, we confirmed that disability progression was independent of relapses and brain MRI activity.

Disability status and dental pathology in multiple sclerosis patients

2015 ◽  
Vol 4 (6) ◽  
pp. 567-571 ◽  
Author(s):  
Adriana Octaviana Dulamea ◽  
Voicu Boscaiu ◽  
Maria Mirela Sava
Keyword(s):  
Multiple Sclerosis ◽  
Dental Pathology ◽  
Disability Status ◽  
Multiple Sclerosis Patients

Therapeutic Effect of Vitamin D3 in Multiple Sclerosis Patients

2011 ◽  
Vol 40 (6) ◽  
pp. 627-639 ◽  
Author(s):  
Ghasem Mosayebi ◽  
Ali Ghazavi ◽  
Keyvan Ghasami ◽  
Yahya Jand ◽  
Parviz Kokhaei
Keyword(s):  
Multiple Sclerosis ◽  
Therapeutic Effect ◽  
Vitamin D3 ◽  
Multiple Sclerosis Patients

scholarly journals Should We Use Clinical Tools to Identify Disease Progression?

2021 ◽  
Vol 11 ◽  
Author(s):  
Hernan Inojosa ◽  
Undine Proschmann ◽  
Katja Akgün ◽  
Tjalf Ziemssen
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Markers ◽  
Disability Progression ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Secondary Progressive ◽  
Disability Status ◽  
Relapsing Remitting ◽  
Clinical Tools

The presence of disability progression in multiple sclerosis (MS) is an important hallmark for MS patients in the course of their disease. The transition from relapsing remitting (RRMS) to secondary progressive forms of the disease (SPMS) represents a significant change in their quality of life and perception of the disease. It could also be a therapeutic key for opportunities, where approaches different from those in the initial phases of the disease can be adopted. The characterization of structural biomarkers (e.g., magnetic resonance imaging or neurofilament light chain) has been proposed to differentiate between both phenotypes. However, there is no definite threshold between them. Whether the risk of clinical progression can be predicted by structural markers at early disease phases is still a focus of clinical research. However, several theories and pathological evidence suggest that both disease phenotypes are part of a continuum with common pathophysiological mechanisms. In this case, the clinical evaluation of the patients would play a preponderant role above destruction biomarkers for the early identification of disability progression and SPMS. For this purpose, the use of clinical tools beyond the Expanded Disability Status Scale (EDSS) should be considered. Besides established functional tests such as the Multiple Sclerosis Functional Composite (MSFC), patient's neurological history or digital resources may help neurologists in the decision-taking. In this article, we discuss arguments for the use of clinical markers in the detection of secondary progressive MS and the characterization of progressive disease activity.

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