Risk Of Sclerosis Research Articles

Association between Genetic Polymorphisms in Methylenetetrahydrofolate Reductase and Risk of Autoimmune Diseases: A Systematic Review and Meta-Analysis.

Methylenetetrahydrofolate reductase (MTHFR) is a critical rate-limiting enzyme in the homocysteine/methionine metabolism pathway that is implicated in the pathogenesis and progression of autoimmune diseases. Previous association studies have been performed to investigate the effect of polymorphisms in MTHFR on the risk of autoimmune diseases with inconsistent results. Therefore, this meta-analysis was designed to assess the association between the MTHFR 677 C/T and 1298 A/C polymorphisms and the susceptibility to autoimmune diseases. We identified reports by a literature search in the following electronic databases: PubMed, Ovid, Web of science, and China National Knowledge Infrastructure. Statistical analyses of the summary odds ratios (ORs) and 95% confidence intervals (CIs) were done using STATA software. In a recessive genetic model, the MTHFR 677 C/T polymorphism was associated with an increased risk of Behcet's disease (OR = 1.97, 95% CI, 1.31-2.97), multiple sclerosis (OR = 1.57, 95% CI, 1.03-2.38), and ankylosing spondylitis (OR = 2.90, 95% CI, 1.92-4.38). The MTHFR 1298 A/C polymorphism was associated an increased risk of multiple sclerosis in a heterozygote comparison (OR = 2.36, 95% CI, 1.29-4.30) and in a dominant model (OR = 2.31, 95% CI, 1.24-4.29). This meta-analysis demonstrated that the MTHFR 677 C/T was a risk factor for Behcet's disease, multiple sclerosis, and ankylosing spondylitis, and the 1298 A/C was a risk factor for multiple sclerosis.

The Effect of Peripheral Immune Cell Counts on the Risk of Multiple Sclerosis: A Mendelian Randomization Study.

ObjectivesMultiple sclerosis (MS) is a complex central nervous system (CNS) demyelinating disease, the etiology of which involves the interplay between genetic and environmental factors. We aimed to determine whether genetically predicted peripheral immune cell counts may have a causal effect on MS.MethodsWe used genetic variants strongly associated with cell counts of circulating leukocyte, lymphocyte, monocyte, neutrophil, eosinophil, and basophil, in addition to some subpopulations of T and B lymphocyte, as instrumental variables (IVs) to perform Mendelian randomization (MR) analyses. The effect of immune cell counts on MS risk was measured using the summary statistics from the International Multiple Sclerosis Genetics Consortium (IMSGC) genome-wide association studies (GWAS).ResultsOur findings indicated that higher leucocyte count [odds ratio (OR), 1.24; 95% confidence interval (CI), 1.07 - 1.43; p = 0.0039] and lymphocyte count (OR, 1.17; 95% CI, 1.01 – 1.35; p = 0.0317) were causally associated with MS susceptibility. In addition, we also found that increase of genetically predicted natural killer T (NKT) cell count is also associated with an increase MS risk (OR, 1.24; 95% CI, 1.06 - 1.45; p = 0.0082).ConclusionsThese findings show that the genetic predisposition to higher peripheral immune cell counts can exert a causal effect on MS risk, which confirms the crucial role played by peripheral immunity in MS. Particularly, the causal association between NKT cell count and MS underscores the relevance of exploring the functional roles of NKT cells in disease pathogenesis in future.

Toll-like receptor 10 gene polymorphism and risk of multiple sclerosis among Iraqi patients

Abstract Background Toll-like receptors (TLRs) are a family of 10 pattern recognition receptors (TLR1–TLR10) involved in the regulation of inflammatory and immune responses besides their role in the pathogenesis of autoimmune diseases including multiple sclerosis (MS). TLR10 is the least studied TLR in MS, and data for single nucleotide polymorphisms (SNPs) of the TLR10 gene are limited. Therefore, a case–control study was performed on 85 patients with relapsing–remitting MS and 86 healthy controls (HC) to explore SNPs in the promoter region of TLR10 gene. A 927-bp region was amplified, and Sanger sequencing identified 10 SNPs with a minor allele frequency ≥ 10% (rs200395112 T/A, rs201802754 A/T, rs201228097 T/A, rs113588825 G/A, rs10004195 T/A, rs10034903 C/G, rs10012016 G/A/C, rs10012017 G/T, rs33994884 T/Deletion [Del] and rs28393318 A/G). Results Del allele and T/Del genotype of rs33994884, as well as AG genotype of rs28393318, showed significantly lower frequencies in MS patients compared to HC. Allele and genotype frequencies of the 10 SNPs showed no significant differences between MS patients classified according to the Expanded Disability Status Scale. Haplotype analysis revealed that haplotype A-T-A-G-A-G-G-T-A showed a significantly increased frequency in MS patients compared to HC (odds ratio [OR] = 9.70; 95% confidence interval [CI] = 1.28–73.31; corrected probability [pc] = 0.03), while frequency of A-T-A-G-T-C-A-T-G haplotype was significantly decreased (OR = 0.10; 95% CI = 0.01–0.85; pc = 0.05). Conclusions The study indicated that two SNPs may influence susceptibility to MS (rs33994884 and rs28393318), but haplotype analysis of TLR10 gene SNPs was more informative.

CSF sTREM2 in neurological diseases: a two-sample Mendelian randomization study

BackgroundSoluble triggering receptor expressed on myeloid cells 2 (sTREM2) in cerebrospinal fluid (CSF) has been described as a biomarker for microglial activation, which were observed increased in a variety of neurological disorders.ObjectiveOur objective was to explore whether genetically determined CSF sTREM2 levels are causally associated with different neurological diseases by conducting a two-sample Mendelian randomization (MR) study.MethodsSingle nucleotide polymorphisms significantly associated with CSF sTREM2 levels were selected as instrumental variables to estimate the causal effects on clinically common neurological diseases, including stroke, Alzheimer’s diseases, Parkinson’s diseases, amyotrophic lateral sclerosis, multiple sclerosis, and epilepsy and their subtypes. Summary-level statistics of both exposure and outcomes were applied in an MR framework.ResultsGenetically predicted per 1 pg/dL increase of CSF sTREM2 levels was associated with higher risk of multiple sclerosis (OR = 1.038, 95%CI = 1.014–1.064, p = 0.002). Null association was found in risk of other included neurological disorders.ConclusionsThese findings provide support for a potential causal relationship between elevated CSF sTREM2 levels and higher risk of multiple sclerosis.

Professional Football Players Are at a Higher Risk for Amyotrophic Lateral Sclerosis

Professional Football Players Are at a Higher Risk for Amyotrophic Lateral Sclerosis

Effect of CoDuSe and step square exercises on risk of fall inmultiple sclerosis: a randomized controlled trial

Objective: Impaired balance and the difficulty to execute dual tasks are common in patients with multiple sclerosis (MS), which are the main causes of risk of fall. The purpose of the study was to determine the effect of a rehabilitation program composed of CoDuSe balance training and step square exercises (SSE) on the risk of fall in MS. Methods: Fifty-two patients with MS were randomly divided into two equal groups; the study group that received CoDuSe balance training and SSE combined with the selected exercise program for four weeks, while the control group received only the selected exercise program. All patients were assessed pre-and post-rehabilitation program with the Biodex Balance System (BBS) using the fall risk index test, Short Physical Performance Battery (SPPB), and Morse Fall Scale (MFS). Results: Comparing groups post-treatment revealed significant reductions in MFS and risk of falls scores (p < 0.05) and a significant increase in balance, gait, lower limb strength, and total scores of SPPB of the study group compared with the control group. Conclusions: The combination of CoDuSe balance training and SSE had a significant effect in reducing the risk of fall and improving balance in patients with MS, thus this treatment program should be considered in MS physical rehabilitation.

Vitamin D and Depressive Symptoms in Adults with Multiple Sclerosis: A Scoping Review

Background. Vitamin D deficiency has been correlated with Multiple Sclerosis (MS) risk and disease activity. There is some controversy as to whether vitamin D could have an impact on depressive symptoms in people with MS (pwMS). The aim of this scoping review was to evaluate the association between vitamin D status and depressive symptoms in pwMS. Methods. We searched databases to include studies published up to March 2021 to provide an overview of the available evidence on the correlation between vitamin D status and depressive symptoms in pwMS. The eligibility criteria were as follows: studies evaluating the use of vitamin D measurement on depressive symptoms in patients suffering from MS, including randomized and non-randomized studies; studies written in English; and studies exploring an adult population over the age of 18. Results. Eleven studies met our inclusion criteria: two of them were abstracts only; the majority were cross-sectional studies; two were prospective longitudinal studies; one was a retrospective cohort study; and one was a randomized placebo-controlled trial (RCT). Of the eleven studies selected, seven showed a potential correlation between low vitamin D levels and depressive symptoms. Conclusion. Future RCT studies should include patients with greater severity of depressive symptoms and should consider confounding factors such as sun exposure and seasonal variation of vitamin D.

Does Bisphosphonate Increase the Sclerosis of Tibial Subchondral Bone in the Progression of Knee Osteoarthritis-A Propensity Score Matching Cohort Study Based on Osteoarthritis Initiative.

Bisphosphonate has great potential in KOA therapy, but whether the anti-resorption mechanism of bisphosphonate aggravates sclerosis of subchondral bone remains unclear. We found that bisphosphonate use did not increase sclerosis of subchondral bone in established KOA, perhaps resolving some concerns about bisphosphonate in patients with KOA.Introduction: Most studies have focused on the protective effect of bisphosphonate on early knee osteoarthritis (KOA) through its anti-resorption mechanism in osteoclasts. However, late KOA has a decreased rate of resorption, which is the opposite of early KOA. The risk of subchondral bone sclerosis in late KOA after using bisphosphonate has not been investigated using morphometry.Methods: Forty-five patients who had ever used bisphosphonate (or 33 patients with current use) were matched with controls through propensity matching methods, including age, body mass index (BMI), sex, health status (12-Item Short Form Survey physical health score), physical activity level (Physical Activity Scale for the Elderly score), vitamin D use, and calcium use. At the baseline and 12-month (or 18-month) follow-up, bone mineral density (BMD) of the tibia and hip was measured by dual-energy X-ray absorptiometry (DXA), and medial tibial subchondral bone morphometry: bone volume fraction (BV/TV), trabecular thickness (Tb.Th), trabecular number (Tb.N), and trabecular separation (Tb.Sp) were calculated based on 3-T trabecular MRI. Data were obtained from the Bone Ancillary Study in the Osteoarthritis Initiative (OAI) project.Results: The yearly percentage change in hip BMD of the current bisphosphonate-use group was significantly greater than that of the non-bisphosphonate-use group (0.7% vs. −1%, P = 0.02). The other outcomes (BV/TV, Tb.N, Tb.Sp, Tb.Th, tibia medial BMD, and tibia lateral BMD) between the two groups presented no significant difference. The non-bisphosphonate-use group experienced a significant increase in Tb.Th [2%, 95% CI = (1%, 4%), P = 0.01], while the bisphosphonate-use group presented no significant change [1%, 95% CI = (−2%, 4%), P = 0.54].Conclusions: Bisphosphonate use did not increase sclerosis of subchondral bone in established KOA. Bisphosphonate might have a stage-dependent effect on subchondral bone in KOA initiation and progression.

Risk of Multiple Sclerosis: Analysis of Interactions between Variants of Nuclear and Mitochondrial Genomes

Risk of Multiple Sclerosis: Analysis of Interactions between Variants of Nuclear and Mitochondrial Genomes

Seasonal variability of serum 25-hydroxyvitamin D on multiple sclerosis onset

Vitamin D deficiency is associated with an increased risk of multiple sclerosis (MS). However, its effect on the age of disease onset remains unclear. This study examines the relationship between serum 25-hydroxyvitamin D (25(OH)D) levels and age of first symptom onset among recently diagnosed MS patients. Serum 25(OH)D was measured from forty MS patients sampled near disease onset. After correcting seasonal variability, the association between 25(OH)D levels, along with other clinical measures such as IgG index, and age at MS onset was examined using multivariable linear regression. Serum 25(OH)D was not correlated with age at onset (P > 0.5). We observed bias among previously reported associations between 25(OH)D and MS disease measures resulting from non-random distribution of sampling by season. After correcting for seasonal 25(OH)D and other clinical measures, only CSF IgG index remained significantly associated with age at disease onset (β = − 5.35, P = 0.028). In summary, we observed no association between age at onset and serum 25(OH)D levels but observed a negative correlation with CSF IgG index, although this will require further investigation.

The relationship of HLA-G 14-bp insertion/deletion genetic polymorphism to the risk of multiple sclerosis and its clinical phenotypes

BackgroundHuman leukocyte antigen (HLA)-G molecule has been suggested to have a potential immunomodulatory role in multiple sclerosis (MS). Genetic variant sites of HLA-G molecule have been reported to be associated with autoimmune diseases. Identifying the genetic risk factors of MS may help in preventive strategies and anticipating disease progression. The aim of this work was to investigate the effect of HLA-G 14-base-pair insertion/deletion (14-bp INS/DEL) genetic polymorphism on MS risk and clinical characteristics and to observe the clinical characteristics of the MS patients’ group. The study included 48 MS patients and 50 cross-matched healthy controls, who were recruited from Sohag and Assiut university hospitals. Genetic testing (14-bp Ins/Del gene polymorphism) using polymerase chain reaction (PCR) was performed for patients and control groups. All patients had a detailed clinical assessment and have undergone measurement of disability using the Expanded Disability Status Scale (EDSS).ResultsNo statistically significant difference was found between MS patients and healthy controls (HC) in genotypic and allelic frequencies of HLA-G 14-bp INS/DEL polymorphism (P=0.305). No significant association was found between HLA-G 14-bp INS/DEL polymorphism genotypes and clinical characteristics or degree of disability of MS patients. The most frequent presenting symptoms of MS were motor symptoms. Fatigue was the most reported symptom along the course of MS disease.ConclusionAlthough it has been long known that HLA-G represents an important MS susceptibility locus, in this study, no significant relation could be detected between the 14-bp INS/DEL polymorphism genotype and MS susceptibility. MS risk susceptibility may be not linked to a single allele but may depend on the combination of different polymorphic genetic sites. In this study, the lack of genetic susceptibility may be attributed to ethnic factor.

Neurological presentations of inflammatory bowel diseases

The aim. To characterize the main types of neurological manifestations in inflammatory bowel diseases – Crohn’s disease and ulcerative colitis.Main concepts. Neurological disorders represent an important aspect of extraintestinal inflammatory bowel diseases (IBD) manifestations. According to publications, the incidence of psycho-neurological syndromes varies from 0.25% to 47.50% that apparently depends on the patient’s selection in studies. Neurological signs are not always associated with IBD activity and may precede the manifestation of intestinal inflammation. The most typical include cerebral thromboembolism, peripheral and cranial neuropathies, demyelinating disorders, and cerebral vasculitis. The incidence of ischemic stroke in IBD can reach 6.4%, with approx. 20% of affected persons under 17 y.o. Hemiparesis is the predominant consequence. The risk of intracranial venous thrombosis is increased depending on the activity of intestinal inflammation; this complication can precede manifestation of IBD. Fifty per cent increased risk of multiple sclerosis in IBD patients was shown. The types of peripheral nerves involvement include mononeuropathy, plexopathy, multiple mononeuropathy, compression neuropathy, polyneuropathy and cranial neuropathy. Peripheral neuropathy may be found in 32–37% of IBD patients with a special examination. Demyelinating type, sensory axonal polyneuropathy with thin and thick fibers damage, and motor axonal polyneuropathy with thick fibers damage are observed approximately in equal proportions. It is important to differentiate ‘primary’ neuropathy with vitamin B12 and folic acid deficient, alcoholic, diabetic and drug-induced neuropathy. Clinical improvement is usually seen in the course of immunosuppressive therapy. Cranial neuropathy (mostly of II, VI, VII, VIII of cranial nerves) is described in IBD. Neurological disorders associated with administration of metronidazole, sulfasalazine, cyclosporin A, antibodies to TNF-α and integrins α4 and α4ß7 continue to be highly actual.Conclusion. There is a variety of neurologic syndromes in IBD which represents an important part of extraintestinal manifestations. Mild psychoneurological disorders may be not recognized in time. The majority of symptoms and signs may regress in the course of treatment of IBD and nutrients deficiency correction. The special attention should be paid to neurological status control while the biologic and immunosuppressor agents and metronidazole are administered.

Iron Status May Not Affect Amyotrophic Lateral Sclerosis: A Mendelian Randomization Study.

BackgroundObservational studies have shown an association of increased iron status with a higher risk of amyotrophic lateral sclerosis (ALS). Iron status might be a novel target for ALS prevention if a causal relationship exists. We aimed to reveal the causality between iron status and ALS incidence using a large two-sample Mendelian randomization (MR).MethodsSingle nucleotide polymorphisms (SNPs) for iron status were identified from a genome-wide association study (GWAS) on 48,972 individuals. The outcome data came from the largest ALS GWAS to date (20,806 cases; 59,804 controls). We conducted conservative analyses (using SNPs with concordant change of biomarkers of iron status) and liberal analyses (using SNPs associated with at least one of the biomarkers of iron status), with inverse variance weighted (IVW) method as the main analysis. We then performed sensitivity analyses including weighted median, MR-Egger and MR-pleiotropy residual sum and outlier, as well as leave-one-out analysis to detect pleiotropy.ResultsIn the conservative analyses, we found no evidence of association between four biomarkers of iron status and ALS using IVW method with odds ratio (OR) 1.00 [95% confidence interval (CI): 0.90–1.11] per standard deviation (SD) increase in iron, 0.96 (95% CI: 0.77–1.21) in ferritin, 0.99 (95% CI: 0.92–1.07) in transferrin saturation, and 1.04 (95% CI: 0.93–1.16) in transferrin. Findings from liberal analyses were similar, and sensitivity analyses suggested no pleiotropy detected (all p > 0.05).ConclusionOur findings suggest no causal effect between iron status and risk of ALS. Efforts to change the iron status to decrease ALS incidence might be impractical.

Neurofilament heavy chain gene polymorphism and risk of multiple sclerosis

Multiple sclerosis (MS) is a chronic disease characterized by degeneration of the central nervous system (CNS). High levels of Neurofilament heavy chain (NEFH) in cerebrospinal fluid (CSF) is associated with MS. 40 MS patients and 40 controls genotyped by polymerase chain reaction (PCR) and Sanger sequencing. Genotypic and allelic distributions were compared between cases and controls. Fisher test was used to estimate the risk of MS associated with genotypes. We showed that NEFH, 1084-244G>A gene polymorphism, has no significant association with the susceptibility or severity of MS in Iranian patients (P = 0.737). Further prospective studies are required for confirmation.

The effectiveness of nonsteroidal anti-inflammatory drugs and acetaminophen in reduce the risk of amyotrophic lateral sclerosis? A meta-analysis

To test the hypothesis that aspirin, non-aspirin nonsteroidal anti-infammatory drugs (NA-NSAIDs), or acetaminophen can reduce the risk of ALS, we conducted a systematic review and meta-analysis of related previous studies. A comprehensive search was conducted on the PubMed, Embase, Cochrane Library and SCOPUS databases. It included studies published up to 29 February 2020 that fulfilled our inclusion criteria. Aspirin, acetaminophen and NA-NSAIDs use information, between the ALS and control groups, was collected for the meta-analysis. Rates of aspirin, NA-NSAID, and acetaminophen use in ALS group, compared with control group were investigated. In the results, only three studies that relate the risk of ALS to aspirin, NA-NSAIDs and acetaminophen use satisfied the inclusion criteria for the meta-analysis. Regarding aspirin, the studies did not show any statistically significant difference in aspirin use between the ALS and control groups (Odds ratio, 1.04 [95% confidence interval, 0.90–1.21]). NA-NSAIDs and acetaminophen use, however, did show up statistically significant differences in between the ALS and control groups. (Odds ratio, 0.82 [95% confidence interval, 0.73–0.91]) and (Odds ratio, 0.80 [95% confidence interval, 0.69–0.93]). However, our study has some limitations. Firstly, we only included a small number of studies. Secondly, the included studies did not control for past medical history, which may have confounded their results, and in turn, could have caused bias in our study. Thirdly, in this meta-analysis, the ALS patients were not subdivided into sporadic or familial type. Lastly, the studies also did not consider the types of NSAIDs and dosages used of each drug. For more convincing evidence regarding the effectiveness of aspirin, NA-NSAIDs and acetaminophen to reduce the risk of ALS occurrence, more qualified prospective studies are required. In conclusion, the use of NA-NSAIDs and acetaminophen is associated with a decreased risk for the development of ALS. In contrast, aspirin did not have any effect on the reduction of the risk of ALS occurrence.

PM2.5 exposure as a risk factor for multiple sclerosis. An ecological study with a Bayesian mapping approach

Some environmental factors are associated with an increased risk of multiple sclerosis (MS). Air pollution could be a main one. This study was conducted to investigate the association of particulate matter 2.5 (PM2.5) concentrations with MS prevalence in the province of Pavia, Italy. The overall MS prevalence in the province of Pavia is 169.4 per 100,000 inhabitants. Spatial ground-level PM2.5 gridded data were analysed, by municipality, for the period 2010–2016. Municipalities were grouped by tertiles according to PM2.5 concentration. Ecological regression and Bayesian statistics were used to analyse the association between PM2.5 concentrations, degree of urbanization, deprivation index and MS risk. MS risk was higher among persons living in areas with an average winter PM2.5 concentration above the European annual limit value (25 μg/m3). The Bayesian map revealed sizeable MS high-risk clusters. The study found a relationship between low MS risk and lower PM2.5 levels, strengthening the suggestion that air pollution may be one of the environmental risk factors for MS.

Functional fine-mapping of noncoding risk variants in amyotrophic lateral sclerosis utilizing convolutional neural network

Recent large-scale genome-wide association studies have identified common genetic variations that may contribute to the risk of amyotrophic lateral sclerosis (ALS). However, pinpointing the risk variants in noncoding regions and underlying biological mechanisms remains a major challenge. Here, we constructed a convolutional neural network model with a large-scale GWAS meta-analysis dataset to unravel functional noncoding variants associated with ALS based on their epigenetic features. After filtering and prioritizing of candidates, we fine-mapped two new risk variants, rs2370964 and rs3093720, on chromosome 3 and 17, respectively. Further analysis revealed that these polymorphisms are associated with the expression level of CX3CR1 and TNFAIP1, and affect the transcription factor binding sites for CTCF, NFATc1 and NR3C1. Our results may provide new insights for ALS pathogenesis, and the proposed research methodology can be applied for other complex diseases as well.

Meta-analysis of the association between CHCHD10 Pro34Ser variant and the risk of amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS), one of the motor neuron diseases, appears to be caused by genetic and environmental risk factors. However, the influence of Pro34Ser variant of CHCHD10 gene in increasing risk of ALS remains indeterminate. This study conducted a meta-analysis to establish the association between Pro34Ser variant of CHCHD10 gene and risk of ALS. PubMed, Web of Science, and Embase databases were systematically searched for genome-wide association studies or case-control studies published up to March 28, 2020, on the association between Pro34Ser variant and risk of ALS. Data from eligible studies were extracted and analyzed. Twelve case-control studies involving 7442 patients with sporadic ALS and 75,371 controls were analyzed. The Pro34Ser variant was not associated with increased risk of ALS disease based on fixed-effects meta-analysis (Pro34Ser-positive vs Pro34Ser-negative: OR 1.23, 95% CI 0.90 to 1.69, P = 0.201). Existing evidence suggests that Pro34Ser variant in CHCHD10 is not associated with risk of ALS, particularly in Caucasian participants. However, our results ought to be validated using large, well-designed studies, especially in Asian and African populations.

Smoking and Epstein\u2013Barr virus infection in multiple sclerosis development

It is unclear whether smoking interacts with different aspects of Epstein–Barr virus (EBV) infection with regard to multiple sclerosis (MS) risk. We aimed to investigate whether smoking acts synergistically with elevated EBNA-1 antibody levels or infectious mononucleosis (IM) history regarding MS risk. Two Swedish population-based case–control studies were used (6,340 cases and 6,219 matched controls). Subjects with different smoking, EBNA-1 and IM status were compared regarding MS risk, by calculating odds ratios (OR) with 95% confidence intervals (CI) employing logistic regression. Potential interaction on the additive scale was evaluated by calculating the attributable proportion due to interaction (AP). Current and past smokers had higher EBNA-1 antibody levels than never smokers (p < 0.0001). There was an additive interaction between current smoking and high EBNA-1 antibody levels (AP 0.3, 95% CI 0.2–0.4), but not between past smoking and high EBNA-1 antibody levels (AP 0.01, 95% CI − 0.1 to 0.1), with regard to MS risk. An interaction also occurred between current smoking and IM history (AP 0.2, 95% CI 0.004–0.4), but not between past smoking and IM history (AP − 0.06, 95% CI − 0.4 to 0.3). Current smoking increases EBNA-1 antibody levels and acts synergistically with both aspects of EBV infection to increase MS risk, indicating that there is at least one pathway to disease in which both risk factors are involved.

Matrix metalloproteinases (MMPs) family gene polymorphisms and the risk of multiple sclerosis: systematic review and meta-analysis

BackgroundSeveral studies have reported the association between polymorphisms in Matrix metalloproteinases (MMPs) gene family and risk of Multiple sclerosis (MS). However, the results have been inconsistent and inconclusive. To resolve this issue, here we performed a systematic review and meta-analysis of the MMP-91562 C/T (rs3918242), MMP-3 (− 1612 5A/6A), and MMP-2 (− 1306 C/T) polymorphisms and susceptibility to MS.MethodsWe conducted a comprehensive systematic search in the major electronic database, including Scopus and PubMed to look up for relevant studies published before December 2019 that surveyed the association between the MMP-91562 C/T (rs3918242), MMP-3 (− 1612 5A/6A), and MMP-2 (− 1306 C/T) polymorphisms and susceptibility to MS. The level of association between the polymorphisms and susceptibility to MS in the polled analysis was determined by calculating the odds ratio (OR) and the corresponding 95% confidence interval (CI).ResultsWe found 15 studies containing 2430 MS subjects and 2304 controls. A statistically significant association was observed in the all five comparisons of the MMP-91562 C/T polymorphism and MS risk as follows: dominant model (OR = 1.62, 95% CI = 1.03–2.53, P = 0.03), recessive model (OR = 2.69, 95% CI = 1.68–4.29, P < 0.001), allelic model (OR = 1.51, 95% CI = 1–2.28, P = 0.04), TT vs. CC model (OR = 3.20, 95% CI = 1.87–5.46, P < 0.001), and CT vs. CC model (OR = 1.53, 95% CI = 1.02–2.28, P = 0.04).ConclusionsOur meta-analysis revealed significant association of MMP-9 (− 1562 C/T) Single-nucleotide polymorphism (SNP) with MS susceptibility that increased the disease risk.