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Vitamin D receptor genetic polymorphisms and the risk of multiple sclerosis: A systematic review and meta-analysis.
Mohammadi, A, Azarnezhad, A, Khanbabaei, H, Izadpanah, E, Abdollahzadeh, R, Barreto, GE, Sahebkar, A
Steroids. 2020;:108615
Abstract
There are conflicting results regarding the exact effect of the vitamin D receptor (VDR) gene polymorphisms on the susceptibility to multiple sclerosis (MS). Therefore, we aimed to investigate the impact of four major studied VDR gene polymorphisms consisting of ApaI, BsmI, FokI, and TaqI on the risk of MS in the Iranian population. A literature search was performed in various databases to find case-control studies evaluating the association between VDR gene polymorphisms and MS risk in Iran. Data were extracted and odds ratios (OR) with 95% confidence intervals (CI) were calculated. Subgroup analyze was performed to detect potential sources of heterogeneity. A total of 1206 cases and 1402 controls in nine case-control studies were included. ApaI was the only variant which showed statistically significant relation in allelic (OR = 0.54 (95% CI: 0.37-0.79); P = 0.00), homozygote (OR = 3.48 (95% CI: 1.7-6.9); P = 0.00), dominant (OR = 0.56 (95% CI: 0.3-0.79); P = 0.01), and recessive (OR = 0.35 (95% CI: 0.18-0.66); P = 0.00) models. The TaqI polymorphism showed a significant negative association with MS only in the homozygote model (OR = 0.28 (95% CI: 0.08-0.9); P = 0.04). The BsmI polymorphism also showed significant relation in allelic (OR = 0.69 (95% CI: 0.51-0.94); P = 0.01), homozygote (OR = 0.46 (95% CI: 0.25-0.86); P = 0.01), and recessive OR = 0.56 (95% CI: 0.39-0.8); P = 0.00) models after performing sensitivity analysis. FokI polymorphism showed no significant association with MS risk. ApaI and TaqI TT genotype were found contributing to MS susceptibility and BsmI and FokI showed no relation with MS susceptibility in the Iranian population.
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2.
Dietary interventions for multiple sclerosis-related outcomes.
Parks, NE, Jackson-Tarlton, CS, Vacchi, L, Merdad, R, Johnston, BC
The Cochrane database of systematic reviews. 2020;(5):CD004192
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Abstract
BACKGROUND Multiple sclerosis (MS) is a common demyelinating disease of the central nervous system. Although the exact pathogenesis remains unknown, the leading theory is that it results from immune system dysregulation. Approved disease-modifying therapy appears to modulate the immune system to improve MS-related outcomes. There is substantial interest in the ability of dietary interventions to influence MS-related outcomes. This is an update of the Cochrane Review 'Dietary interventions for multiple sclerosis' (Farinotti 2003; Farinotti 2007; Farinotti 2012). OBJECTIVES To assess the effects of dietary interventions (including dietary plans with recommendations for specific whole foods, macronutrients, and natural health products) compared to placebo or another intervention on health outcomes (including MS-related outcomes and serious adverse events) in people with MS. SEARCH METHODS On 30 May 2019, we searched CENTRAL, MEDLINE, Embase, and Web of Science. We also searched ClinicalTrials.gov, World Health Organization International Clinical Trials Registry Platform (ICTRP), and Networked Digital Library of Theses and Dissertations (NDLTD). We checked reference lists in identified trials and requested information from trial authors to identify any additional published or unpublished data. SELECTION CRITERIA We included any randomized controlled trial (RCT) or controlled clinical trial (CCT) examining the effect of a dietary intervention versus placebo or another intervention among participants with MS on MS-related outcomes, including relapses, disability progression, and magnetic resonance imaging (MRI) measures. DATA COLLECTION AND ANALYSIS We used standard methodological procedures expected by Cochrane. Planned primary outcomes were number of participants experiencing relapse and change in disability progression, according to a validated disability scale at the last reported follow-up. Secondary outcomes included MRI activity, safety, and patient-reported outcomes. We entered and analysed data in Review Manager 5. MAIN RESULTS We found 41 full-text articles examining 30 trials following full-text review. Participants were adults with MS, defined by established criteria, presenting to MS clinics in Europe, North America, and the Middle East. Study design varied considerably, although all trials had at least one methodological issue leading to unknown or high risk of bias. Trials examined: supplementation to increase polyunsaturated fatty acids (PUFAs) (11 trials); a variety of antioxidant supplements (10 trials); dietary programmes (3 trials); and other dietary supplements (e.g. acetyl L-carnitine, biotin, creatine, palmitoylethanolamide, probiotic, riboflavin) (6 trials). In three trials comparing PUFAs with monounsaturated fatty acids (MUFAs), the evidence was very uncertain concerning difference in relapses (risk ratio (RR) 1.02, 95% confidence interval (CI) 0.88 to 1.20; 3 studies, 217 participants; 75% in the PUFA group versus 74% in the MUFA group; very low-certainty evidence). Among four trials comparing PUFAs with MUFAs, there may be little to no difference in global impression of deterioration (RR 0.85, 95% CI 0.71 to 1.03; 4 studies, 542 participants; 40% in the PUFA group versus 47% in the MUFA group; low-certainty evidence). In two trials comparing PUFAs with MUFAs (102 participants), there was very low-certainty evidence for change in disability progression. None of the PUFA versus MUFA trials examined MRI outcomes. In one trial comparing PUFAs with MUFAs (40 participants), there were no serious adverse events; based on low-certainty evidence. In two trials comparing different PUFAs (omega-3 versus omega-6), there may be little to no difference in relapses (RR 1.02, 95% CI 0.62 to 1.66; 2 studies, 129 participants; 30% in the omega-3 versus 29% in the omega-6 group; low-certainty evidence). Among three trials comparing omega-3 with omega-6, there may be little to no difference in change in disability progression, measured as mean change in Expanded Disability Status Scale (EDSS) (mean difference (MD) 0.00, 95% CI -0.30 to 0.30; 3 studies, 166 participants; low-certainty evidence). In one trial comparing omega-3 with omega-6, there was likely no difference in global impression of deterioration (RR 0.99, 95% CI 0.51 to 1.91; 1 study, 86 participants; 29% in omega-3 versus 29% in omega-6 group; moderate-certainty evidence). In one trial comparing omega-3 with omega-6 (86 participants), there was likely no difference in number of new T1- weighted gadolinium-enhancing lesions, based on moderate-certainty evidence. In four trials comparing omega-3 with omega-6, there may be little to no difference in serious adverse events (RR 1.12, 95% CI 0.38 to 3.31; 4 studies, 230 participants; 6% in omega-3 versus 5% in omega-6 group; low-certainty evidence). In four trials examining antioxidant supplementation with placebo, there may be little to no difference in relapses (RR 0.98, 95% CI 0.59 to 1.64; 4 studies, 345 participants; 17% in the antioxidant group versus 17% in the placebo group; low-certainty evidence). In six trials examining antioxidant supplementation with placebo, the evidence was very uncertain concerning change in disability progression, measured as mean change of EDSS (MD -0.19, 95% CI -0.49 to 0.11; 6 studies, 490 participants; very low-certainty evidence). In two trials examining antioxidant supplementation with placebo, there may be little to no difference in global impression of deterioration (RR 0.99, 95% 0.50 to 1.93; 2 studies, 190 participants; 15% in the antioxidant group versus 15% in the placebo group; low-certainty evidence). In two trials examining antioxidant supplementation with placebo, the evidence was very uncertain concerning difference in gadolinium-enhancing lesions (RR 0.67, 95% CI 0.09 to 4.88; 2 studies, 131 participants; 11% in the antioxidant group versus 16% in the placebo group; very low-certainty evidence). In three trials examining antioxidant supplementation versus placebo, there may be little to no difference in serious adverse events (RR. 0.72, 95% CI 0.17 to 3.08; 3 studies, 222 participants; 3% in the antioxidant group versus 4% in the placebo group; low-certainty evidence). AUTHORS' CONCLUSIONS There are a variety of controlled trials addressing the effects of dietary interventions for MS with substantial variation in active treatment, comparator, and outcomes of interest. PUFA administration may not differ when compared to alternatives with regards to relapse rate, disability worsening, or overall clinical status in people with MS, but evidence is uncertain. Similarly, at present, there is insufficient evidence to determine whether supplementation with antioxidants or other dietary interventions have any impact on MS-related outcomes.
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Association between CD24 Ala/Val polymorphism and multiple sclerosis risk: A meta analysis.
Yang, W, Zhou, W, Zhang, BK, Kong, LS, Zhu, XX, Wang, RX, Yang, Y, Chen, YF, Chen, LR
Medicine. 2020;(15):e19530
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Abstract
BACKGROUND The aim of this study was to explore the association between CD24 Ala/Val polymorphism and susceptibility of multiple sclerosis (MS). METHODS A comprehensive literature search for relevant studies was performed on google scholar, PubMed, Web of science, Embase, the Chinese National Knowledge Infrastructure and the Chinese Biology Medicine. This meta-analysis was conducted using the STATA 11.0 software and the pooled odds ratio with 95% confidence interval was calculated. RESULTS Seven case-control studies were included in this meta-analysis. The results showed significant association between CD24 Ala/Val polymorphism and susceptibility to MS. Stratified analysis by areas also showed significant association in Asians. However, no association was found in Europeans. CONCLUSION This study suggested that the CD24 Val allele was associated with an increased risk of MS and larger-scale studies of populations are needed to explore the role of CD24 Ala/Val polymorphism during the pathogenesis of MS.
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Effects of Fampridine in People with Multiple Sclerosis: A Systematic Review and Meta-analysis.
Valet, M, Quoilin, M, Lejeune, T, Stoquart, G, Van Pesch, V, El Sankari, S, Detrembleur, C, Warlop, T
CNS drugs. 2019;(11):1087-1099
Abstract
BACKGROUND Prolonged-release (PR) fampridine is a potassium channel blocker used as a symptomatic treatment for walking disability in patients with multiple sclerosis (MS). Its clinical effects in such patients have not been systematically reviewed, and may be more wide-ranging than expected. OBJECTIVES To summarize the evidence on the effects of PR fampridine in patients with MS. METHODS A systematic search of Pubmed, Scopus (including EMBASE), and PsycINFO (completed in 01/2019) was carried out to identify randomized controlled trials (RCT) that compared PR fampridine to placebo. When appropriate, data were pooled using a random-effects model, and standardized mean differences (SMD) were computed. Study quality was assessed using the Downs and Black checklist. PRISMA guidelines were followed. All retrieved functional outcomes were categorized according to the International Classification of Functioning, Disability and Health (ICF). RESULTS A total of 706 articles were screened for inclusion. Twenty RCTs involving 2616 patients met the eligibility criteria. Most studies were of good-to-excellent quality. PR fampridine administration resulted in significant benefits in relation to walking short distances (SMD: 1.23 (95% IC 0.65-1.81)) and perceived walking capacity (0.64 (0.27-1.02)). Its effects on muscle strength and middle-distance walking were not significant (0.53 (- 0.04 to 1.10) and 0.31 (- 0.18 to 0.80), respectively). No effect on higher-level cognitive functions (- 0.07 (- 0.58 to 0.45)) or hand and arm use (0.16 (- 0.33 to 0.64)) was observed. Individual studies reported effects on other outcomes across the ICF domains. CONCLUSIONS There is strong evidence that PR fampridine exerts strong effects on the ability to walk short distances and on perceived walking capacity. Other effects of PR fampridine according to the ICF are possible but still unclear.
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Association of Vitamin D Receptor Gene Polymorphisms and the Risk of Multiple Sclerosis: A Meta Analysis.
Zhang, D, Wang, L, Zhang, R, Li, S
Archives of medical research. 2019;(6):350-361
Abstract
BACKGROUND Previous studies have reported vitamin D receptor (VDR) polymorphisms in multiple sclerosis (MS); however, the results remain contradictory. This study aimed to investigate the association between VDR polymorphisms and the risk of MS. METHODS PubMed and Embase databases were searched to obtain eligible studies. Data were calculated by odds ratios (OR) with 95% confidence intervals (CI). RESULTS Twenty seven case-control studies with 4879 MS patients and 5402 controls were included. There was no significant association between ApaI polymorphisms and MS in the overall population. In Asians, no association was found between ApaI polymorphism and MS in the recessive, dominant, Codominant (OR1), Codominant (OR2), Codominant (OR3) models and allele contrast. Similar results were obtained between BsmI polymorphisms and MS. The association between TaqI polymorphism and MS showed significance in the recessive, homozygous, codominant (OR3) models in the overall population and Caucasians. The dominant model showed no association of Taq I polymorphism with MS risk in HLA-DRB1*15-positive and HLA-DRB1*15-negative groups. FokI polymorphism with MS was found in Codominant (OR3) model in the overall population. In Asians, FokI polymorphism showed association with MS in recessive, dominant, Codominant (OR1), Codominant (OR3) models and allele contrast. Subgroup analysis of sex showed no associations between TaqI or FokI polymorphism and MS risk in males or females in all models or allele contrast. CONCLUSIONS The VDR TaqI polymorphisms showed association with MS risk, especially in Caucasians. In Asians, ApaI and FokI polymorphisms correlated with MS risk, while BsmI polymorphisms showed no association with MS.
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The effects of vitamin D supplementation on expanded disability status scale in people with multiple sclerosis: A critical, systematic review and metaanalysis of randomized controlled trials.
Doosti-Irani, A, Tamtaji, OR, Mansournia, MA, Ghayour-Mobarhan, M, Ferns, G, Daneshvar Kakhaki, R, Rezaei Shahmirzadi, A, Asemi, Z
Clinical neurology and neurosurgery. 2019;:105564
Abstract
In this meta-analysis of randomized controlled trials (RCTs), the effects of vitamin D supplementation on the scores for the expanded disability status scale (EDSS) in people with multiple sclerosis (MS) are assessed. The following databases were search up to January 2018: MEDLINE, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials. The quality of the relevant extracted data was assessed according to the Cochrane risk of bias tool. Data were pooled by the use of the inverse variance method and expressed as mean difference with 95% Confidence Intervals (95% CI). Six studies were included in this meta-analysis. The findings demonstrated that supplementation with vitamin D alone and vitamin D plus calcium did not affect the EDSS score (WMD -0.11 (-0.33, 0.11); P = 0.32). In addition, subgroup analysis showed that vitamin D supplementation alone, when compared to the use of a placebo, and vitamin D plus calcium supplementation compared with the control did not affect EDSS (WMD -0.13 (-0.30, 0.11); P = 0.29) and (WMD -0.08 (-0.57, 0.41); P = 0.29), respectively. Overall, this meta-analysis indicated that taking vitamin D in people with MS had no significant effect on EDSS.
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Association between vitamin D receptor (VDR) polymorphisms and the risk of multiple sclerosis (MS): an updated meta-analysis.
Imani, D, Razi, B, Motallebnezhad, M, Rezaei, R
BMC neurology. 2019;(1):339
Abstract
BACKGROUND The association between the Vitamin D Receptor (VDR) gene polymorphism and the risk of Multiple sclerosis (MS) has been evaluated in several researches. However, the findings were inconsistent and inconclusive. Therefore, we set out a meta-analysis of all eligible published case-control studies to obtain an exact evaluation of the association between VDR gene polymorphisms and MS. METHOD All relevant studies reporting the association between the VDR gene FokI (rs2228570), or/and TaqI (rs731236) or/and BsmI (rs1544410) or/and ApaI (rs7975232) polymorphisms and susceptibility to MS published up to May, 2019 were identified by comprehensive systematic search in the electronic database of web of science, Scopus, and PubMed. After that, the strength of association between VDR gene polymorphisms and susceptibility to MS was evaluated by odds ratio (OR) and 95% confidence interval (CI). RESULTS A total of 30 case-control studies were included in the meta-analysis. The overall results suggested a significant association between TaqI polymorphism and MS risk under heterozygote genetic model (OR = 1.27, 95%CI = 1.01-1.59, random effect). Moreover, the pooled results of subgroup analysis declined presence of significant association under all defined genetic model. In subgroup analysis, BsmI polymorphisms was associated with increased risk of MS under recessive model in Asian populations. On the other hand, ApaI polymorphism was associated with decreased risk of MS under recessive and aa vs. AA model in Asian populations. CONCLUSION This meta-analysis suggested a significant association between TaqI polymorphism and MS susceptibility. Furthermore, BsmI polymorphism was associated with increased risk of MS in Asian populations. In contrast, ApaI polymorphism was associated with decreased risk of MS in Asian populations. Future large-scale studies on gene-environment and gene-gene interactions are required to estimate risk factors and assist early diagnosis of patients at high risk for MS.
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Vitamin D in early life and later risk of multiple sclerosis-A systematic review, meta-analysis.
Ismailova, K, Poudel, P, Parlesak, A, Frederiksen, P, Heitmann, BL
PloS one. 2019;(8):e0221645
Abstract
The study examined results from previous studies of early life vitamin D exposure and risk of MS in adulthood, including studies on season or month of birth and of migration. A systematic review was conducted using PubMed and Web of Science databases as well as checking references cited in articles. The quality of studies was assessed using the Newcastle-Ottawa scale and the AMSTAR score. Twenty-eight studies were selected for analysis. Of these, six population studies investigated early life vitamin D exposure and risk of MS, and three found inverse while the remaining found no associations. A consistent seasonal tendency for MS seemed evident from 11/15 studies, finding a reduced occurrence of MS for Northern hemisphere children who were born late autumn, and late fall for children born in the Southern hemisphere. This was also confirmed by pooled analysis of 6/15 studies. Results of the migration studies showed an increased risk of MS if migration from high to low-MS-risk areas had occurred after age 15 years, while risk of MS was reduced for those migrating earlier in life (<15years). A similar, but inverse risk pattern was observed among migrants from low to high-MS-risk areas. One study found an increased risk of MS in the second generation of migrants when migrating from low to high-MS-risk areas. An association between early life vitamin D and later risk of MS seems possible, however evidence is still insufficient to conclude that low vitamin D exposure in early life increases the risk of MS in adulthood. PROSPERO register number: CRD 42016043229.
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Association between VDR polymorphisms and multiple sclerosis: systematic review and updated meta-analysis of case-control studies.
Zhang, YJ, Zhang, L, Chen, SY, Yang, GJ, Huang, XL, Duan, Y, Yang, LJ, Ye, DQ, Wang, J
Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology. 2018;(2):225-234
Abstract
Vitamin D receptor (VDR) polymorphisms have been inconsistently investigated in multiple sclerosis (MS). However, published studies demonstrated differences concerning design and effect size. A meta-analysis is necessary to determine the magnitude of the association between VDR polymorphisms and MS risk. The aim of the current study was to quantify the magnitude of the association between BsmI, FokI, ApaI, and TaqI VDR polymorphisms and MS risk. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we conducted a systematic search and meta-analysis of the VDR gene polymorphisms and the risk of MS. The pooled odds ratios (OR) and 95% confidence interval (CI) were calculated by using Stata Version 11.0 with dominant and recessive models and allele analyses. A total of 4013 cases and 4218 controls in 24 case-control studies were included in the meta-analyses. The results did not indicate an association between any of the VDR polymorphisms and the risk of MS among overall populations, Asians, and Caucasians. However, our subgroup analysis suggests that the A allele was associated with MS risk in Asian populations (P = 0.005, OR = 1.267, 95% CI 1.074-1.496). Interestingly, the sensitivity analysis excluding studies with controls not in HWE showed insignificant association between the A allele and MS risk (P = 0.211), which was different from those in the non-sensitivity analysis. Our preliminary results indicate the VDR gene ApaI, BsmI, FokI, and TaqI polymorphisms may not be associated with elevated MS risk among overall populations. But ApaI polymorphism may confer different susceptibility to MS among different populations, and more well-designed studies with a large sample size are still needed to validate our results.
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Vitamin D for the treatment of multiple sclerosis: a meta-analysis.
McLaughlin, L, Clarke, L, Khalilidehkordi, E, Butzkueven, H, Taylor, B, Broadley, SA
Journal of neurology. 2018;(12):2893-2905
Abstract
OBJECTIVE There is an association between latitude, relative vitamin D deficiency and risk of multiple sclerosis (MS), and an association between vitamin D and disease progression. We have performed a meta-analysis with the aim of investigating the role of therapeutic vitamin D in MS. METHODS A systematic search of databases was performed to identify clinical trials assessing vitamin D in patients with relapsing-remitting MS. Studies were selected based on inclusion and exclusion criteria. Analysis was performed using RevMan 5.3 software. RESULTS Twelve studies involving 950 patients were included in the final analysis. Studies were divided into four groups because of heterogeneity in study design. Studies were judged to be at low or unclear risk of bias, except in three studies, and this was confirmed by funnel plots. No statistically significant difference was seen for any of the outcome measures. There were non-significant trends in favour of vitamin D for all outcome measures, particularly when only placebo-controlled studies were included. Dose comparison studies showed a significant increase in annualised relapse rate (mean difference 0.15 [95%CI 0.01-0.30]) and non-significant trends of increased Expanded Disability Status Scale and gadolinium-enhancing lesions for the higher-dose arms. CONCLUSION These findings suggest that vitamin D supplementation may have a therapeutic role in the treatment of MS. However, there is uncertainty with regard to the most appropriate dose, with high doses potentially being associated with worse outcomes. There remains the need for further well-performed randomised, dose-ranging, placebo-controlled trials of vitamin D in MS.