High Risk For Multiple Sclerosis Research Articles

Evaluation of the Frequency of (rs2227981 and rs2282055) Single Nucleotide Polymorphisms in Programmed Cell Death 1 and Its Ligand Genes of Iraqi Patients With Multiple Sclerosis

Abstract Multiple sclerosis (MS) is a central nervous system disease that causes demyelination and persistent inflammation and most of them among young adults. The current study aimed to assess gene polymorphism of PDCD1 and PDLCD1 genes and the frequency of two SNPs (rs2227981 and rs2282055). MS patients (n=100) were divided into two groups; newly diagnosed (42), and patients with ongoing treatments (58). These groups were compared to healthy subjects (n=55); the mean age ±SD was (30±8.46 years), (37±8.06years), and (31±8.73 years) for MS newly patients, patients with ongoing treatments, and healthy subjects, respectively. Studies for gene polymorphism of PDCD1 and PDLCD1 Genes and the Frequency of Two SNPs (rs2227981 and rs2282055) were measured by Real-time PCR by used HRM. The results of this study found that the genotypic frequencies of MS patient were 31% (n=31) normal AA and 48 % (n=48) heterozygous AG. Mutant homozygous was found in GG 21 % (n=21). In controls, the results demonstrate 69% (n=38) wild type AA, 27.27% (n=15) heterozygous AG and mutant homozygous GG 3.6% (n=2). The odds ratio for the GG genotype was 12.8 (0.2-5.9) with p=0.001 indicating that the homomutant genotype In PD1 gene polymorphism rs2227981 GG was a higher risk of MS than the wild-type PD1 gene polymorphism rs2227981 AA, The PD1 gene polymorphism rs2227981 AG genotype has the second risk of MS after PD1 gene polymorphism rs2227981GG with 3.92 fold high risk than the wild type AA (OR =3.92 (1.8-8.2) p=0.0003). The present study concludes that the population-based case-control study, which focused on the three PD-1 SNPs PD-1.3, PD-1.5, and PD-1.9, found that polymorphism variation might actually be a disease-modifying factor as opposed to an MS risk factor. There were substantially more PD-L1 gene SNP loci in MS patients compared to controls, and there were significantly more PD-L1 gene SNP loci in MS patients compared to controls. The pathogenesis of MS might be connected to PD-1 and PD-L1 SNPs. PD-L1 gene SNP locus rs2282055 and PD-1 gene SNP locus rs2227981 might be potential MS candidate polymorphism loci.

Proportion of Life Spent in Canada and the Incidence of Multiple Sclerosis in Permanent Immigrants.

While immigrants to high-income countries have a lower risk of multiple sclerosis (MS) compared with host populations, it is unknown whether this lower risk among immigrants increases over time. Our objective was to evaluate the association between proportion of life spent in Canada and the hazard of incident MS in Canadian immigrants. We conducted a population-based retrospective cohort study in Ontario, using linked health administrative databases. We followed immigrants, who arrived in Ontario between 1985 and 2003, from January 1, 2003, to December 31, 2016, to record incident MS using a validated algorithm based on hospital admission or outpatient visits. We derived proportion of life spent in Canada based on age at arrival and time since immigration obtained from linked immigration records. We used multivariable proportional hazard models, adjusting for demographics and comorbidities, to evaluate the association between proportion of life in Canada and the incidence of MS, where proportion of life was modelled using restricted cubic spline terms. We further evaluated the role of age at migration (15 or younger vs older than 15 years), sex, and immigration class in sensitivity analyses. We included 1.5 million immigrants (49.9% female, mean age 35.9 [SD 14.2] years) who had spent a median of 20% (Q1-Q3 10%-30%) of their life in Canada. During a mean follow-up of 13.9 years (SD 1.0), 934 (0.44/100,000 person-years) were diagnosed with MS. Compared with the median, a higher risk of MS was observed at higher values of proportion of life spent (e.g., hazard ratio [70% vs 20% proportion of life] 1.38; 1.07-1.78). This association did not vary by sex (p(sex × proportion of life) = 0.70) or immigration class (p(immigration class × proportion of life) = 0.13). The results did not vary by age at migration but were statistically significant only at higher values of proportion of life for immigrants aged 15 years or younger at arrival. The risk of incident MS in immigrants varied with the proportion of life spent in Canada, suggesting an acculturation effect on MS risk. Further work is required to understand environmental and sociocultural factors driving the observed association.

Serologic Response to the Epstein-Barr Virus Peptidome and the Risk for Multiple Sclerosis

It remains unclear why only a small proportion of individuals infected with the Epstein-Barr virus (EBV) develop multiple sclerosis (MS) and what the underlying mechanisms are. To assess the serologic response to all EBV peptides before the first symptoms of MS occur, determine whether the disease is associated with a distinct immune response to EBV, and evaluate whether specific EBV epitopes drive this response. In this prospective, nested case-control study, individuals were selected among US military personnel with serum samples stored in the US Department of Defense Serum Repository. Individuals with MS had serum collected at a median 1 year before onset (reported to the military in 2000-2011) and were matched to controls for age, sex, race and ethnicity, blood collection, and military branch. No individuals were excluded. The data were analyzed between September 1, 2022, and August 31, 2023. Antibodies (enrichment z scores) to the human virome measured using VirScan (phage-displayed immunoprecipitation and sequencing). Rate ratios (RRs) for MS for antibodies to 2263 EBV peptides (the EBV peptidome) were estimated using conditional logistic regression, adjusting for total anti-EBV nuclear antigen 1 (EBNA-1) antibodies, which have consistently been associated with a higher MS risk. The role of antibodies against other viral peptides was also explored. A total of 30 individuals with MS were matched with 30 controls. Mean (SD) age at sample collection was 27.8 (6.5) years; 46 of 60 participants (76.7%) were male. The antibody response to the EBV peptidome was stronger in individuals with MS, but without a discernible pattern. The antibody responses to 66 EBV peptides, the majority mapping to EBNA antigens, were significantly higher in preonset sera from individuals with MS (RR of highest vs lowest tertile of antibody enrichment, 33.4; 95% CI, 2.5-448.4; P for trend = .008). Higher total anti-EBNA-1 antibodies were also associated with an elevated MS risk (top vs bottom tertile: RR, 27.6; 95% CI, 2.3-327.6; P for trend = .008). After adjusting for total anti-EBNA-1 antibodies, risk estimates from most EBV peptides analyses were attenuated, with 4 remaining significantly associated with MS, the strongest within EBNA-6/EBNA-3C, while the association between total anti-EBNA-1 antibodies and MS persisted. These findings suggest that antibody response to EBNA-1 may be the strongest serologic risk factor for MS. No single EBV peptide stood out as being selectively targeted in individuals with MS but not controls. Larger investigations are needed to explore possible heterogeneity of anti-EBV humoral immunity in MS.

Epidemiology of aquaporin-4-IgG-positive NMOSD in Sardinia

PurposeThe Italian Island of Sardinia (population, 1,578,146) is recognized for the high risk of multiple sclerosis (MS) but the epidemiological burden of other less common demyelinating diseases of the central nervous system (CNS), such as aquaporin-4-IgG-positive neuromyelitis optica spectrum disorder (AQP4-IgG+NMOSD), is unknown. In this study, we determined the incidence and prevalence of AQP4-IgG+NMOSD in Sardinia over a ten-year study period (2013–2022). MethodsPatients with a diagnosis of AQP4-IgG+NMOSD (per 2015 IPND diagnostic criteria) were retrospectively identified using two sources: (1) Archives of the reference and only laboratory for AQP4-IgG testing in Sardinia; and (2) medical records of the four MS units in the island. Incidence (January 2013–December 2022) and prevalence (December 31, 2022) were calculated. ResultsA total of 45 cases were included: incident, 31; prevalent, 41. The median age (range) at disease presentation was 51 (6–78) years; female/male ratio was 9:1. The crude (95 % CI) incidence and prevalence were 1.9 (1.3–2.7) per million and 2.6 (1.9–3.5) per 100,000, respectively. Prevalence increased from 2013 (1.1 per 100,000) to 2022 (2.6 per 100,000); p = 0.002. After age-standardization to the world, incidence and prevalence (95 % CI) decreased to 1.3 (0.7–2) per million and 1.8 (1.3–2.3) per 100,000, respectively. Coexisting immune-mediated disorders, mostly autoimmune thyroiditis, were reported in 50 % of patients. ConclusionsThe epidemiology of AQP4-IgG+NMOSD in Sardinia is overall in line with other Caucasian populations. The high MS risk in the island seems disease-specific and not associated with an increased risk of other CNS demyelinating disorders, confirming different pathophysiology.

Vitamin D3 as an add-on treatment for multiple sclerosis: A systematic review and meta-analysis of randomized controlled trials

BackgroundVitamin D deficiency has been linked to a higher risk of multiple sclerosis (MS) and disease progression. However, the efficacy of vitamin D3 as an adjuvant therapy for MS remains a controversial topic. ObjectiveTo perform a systematic review and meta-analysis of randomized controlled trials to assess the impact of adjunct high-dose vitamin D3 on clinical and radiological outcomes. MethodsPubMed, Embase, and Cochrane Library were searched for trials published until December 18th, 2022. Authors independently selected randomized controlled trials involving patients with MS, with an intervention group receiving high dose (≥ 1000 IU/day) cholecalciferol and reporting clinical or radiological outcomes. Authors independently extracted data and assessed the risk of bias using a standardized, pilot-tested form. The meta-analysis was conducted using RStudio for EDSS at the last follow-up, ARR, and new T2 lesion count. ResultsWe included 9 studies with 867 participants. No significant reduction of EDSS (MD = 0.02, CI 95 % [–0.37; 0.41], p = 0.91), ARR (MD –0.03, CI 95 % [–0.08; 0.02], p = 0.26), or new T2 lesions (MD –0.59, CI 95 % [-1.24;0.07], p = 0.08) was observed at 6–24 months. We found no evidence of publication bias. ConclusionThe findings of this meta-analysis strengthen current evidence that vitamin D3 supplementation has no significant impact on clinical outcomes in patients with MS. However, the non-significant reduction of new T2 lesions could precede long-term clinical benefits and should be validated in additional studies.

Association between dental amalgam fillings and multiple sclerosis: A systematic review and meta-analysis

Introduction: Mercury is a neurotoxic element that is released from dental amalgam restorations. Since circumstantial evidence exists that the pathology of multiple sclerosis (MS) disease might be in part caused or exacerbated by inorganic mercury, we conducted a systematic review and meta-analysis using a comprehensive search strategy. Methods: Data bases (PubMed, Google scholar, Cochrane, Embase, Scopus, Ovid, Proquest, and Web of Science) were searched systematically to find the relationship between dental amalgam and MS. Studies were screened according to a pre-defined protocol. The quality of the articles was evaluated by two individuals. The titles and abstracts of the articles were organized and duplicate articles were discovered with the help of Endnote X5 resource management software. Finally, 6 articles were included in the meta-analysis. Random effect model was chosen to conduct the meta-analysis. Results: Pooled mean difference of restoration numbers between two groups was 0.58 (95% CI: 0.33-0.83, P value<0.001) with greater numbers in MS patients. The pooled OR was 1.02 (95% CI, 0.86-1021, P=0.81), which was slightly higher for those with amalgam so they were more likely to develop MS. This slight increase in risk was not statistically significant. Conclusion: Although those who underwent a large number of amalgam fillings were at higher risk for MS, the difference between the two groups of patients and controls was statistically insignificant. It seems that the number of amalgam fillings can be an influential factor in the possibility of developing MS.

A metabolome-wide Mendelian randomization study prioritizes potential causal circulating metabolites for multiple sclerosis

To prioritize circulating metabolites that likely play causal roles in the pathogenesis of multiple sclerosis (MS). Two-sample Mendelian randomization analysis was performed to estimate the causal effects of 571 circulating metabolites on the risk of MS. Genetic instruments for circulating metabolites were obtained from three previous genome-wide association studies (GWAS) of the blood metabolome (N = 7824; 24,925; and 115,078; respectively), while genetic associations with MS were from a large GWAS by the International Multiple Sclerosis Genetics Consortium (14,802 cases and 26,703 control). The primary analysis was performed with the multiplicative random-effect inverse variance-weighted method, while multiple sensitivity analyses were conducted with the weighted median, weighted mode, MR-Egger, and MR-PRESSO. A total of 29 metabolites had suggestive evidence of causal associations with MS. Genetically instrumented levels of serine (OR = 1.56, 95% CI = 1.25–1.95), lysine (OR = 1.18, 95% CI = 1.01–1.38), acetone (OR = 2.45, 95% CI = 1.02–5.90), and acetoacetate (OR = 2.47, 95% CI = 1.14–5.34) were associated with a higher MS risk. Total cholesterol and phospholipids in large very-low-density lipoprotein were associated with a lower MS risk (OR = 0.83, 95% CI = 0.69–1.00; OR = 0.80, 95% CI = 0.68–0.95), but risk-increasing associations (OR = 1.20, 95% CI = 1.04–1.40; OR = 1.13, 95% CI = 1.00–1.28) were observed for the same two lipids in very large high-density lipoprotein. Our metabolome-wide Mendelian randomization study prioritized a list of circulating metabolites, such as serine, lysine, acetone, acetoacetate, and lipids, that likely have causal associations with MS.

Multisite chronic pain and the risk of autoimmune diseases: A Mendelian randomization study.

Accumulating evidence has demonstrated that an association between chronic pain and autoimmune diseases (AIDs). Nevertheless, it is unclear whether these associations refer to a causal relationship. We used a two-sample Mendelian randomization (MR) method to determine the causal relationship between chronic pain and AIDs. We assessed genome-wide association study (GWAS) summary statistics for chronic pain [multisite chronic pain (MCP) and chronic widespread pain (CWP)], and eight common AIDs, namely, amyotrophic lateral sclerosis (ALS), celiac disease (CeD), inflammatory bowel disease (IBD), multiple sclerosis (MS), rheumatoid arthritis (RA), systemic lupus Erythematosus (SLE), type 1 diabetes (T1D) and psoriasis. Summary statistics data were from publicly available and relatively large-scale GWAS meta-analyses to date. The two-sample MR analyses were first performed to identify the causal effect of chronic pain on AIDs. The two-step MR and multivariable MR were used to determine if mediators (BMI and smoking) causally mediated any connection and to estimate the proportion of the association mediated by these factors combined. With the utilization of MR analysis, multisite chronic pain was associated with a higher risk of MS [odds ratio (OR) = 1.59, 95% confidence interval (CI) = 1.01-2.49, P = 0.044] and RA (OR = 1.72, 95% CI = 1.06-2.77, P = 0.028). However, multisite chronic pain had no significant effect on ALS (OR = 1.26, 95% CI = 0.92-1.71, P = 0.150), CeD (OR = 0.24, 95% CI = 0.02-3.64, P = 0.303), IBD (OR = 0.46, 95% CI = 0.09-2.27, P = 0.338), SLE (OR = 1.78, 95% CI = 0.82-3.88, P = 0.144), T1D (OR = 1.15, 95% CI = 0.65-2.02, P = 0.627) or Psoriasis (OR = 1.59, 95% CI = 0.22-11.26, P = 0.644). We also found positive causal effects of MCP on BMI and causal effects of BMI on MS and RA. Moreover, there were no causal connections between genetically predicted chronic widespread pain and the risk of most types of AIDs disease. Our MR analysis implied a causal relationship between MCP and MS/RA, and the effect of MCP on MS and RA may be partially mediated by BMI.

Personality Traits Predict 7-Year Risk of Diagnosis of Multiple Sclerosis: A Prospective Study.

Objective: The objective of the current study is to investigate how Big Five personality traits could predict the risk of multiple sclerosis (MS) diagnosis in 7 years. Methods: A binary logistic regression was used to analyze data from 17,791 participants who responded to questions at Wave 3 (collected between 2011 to 2012) and Wave 10 (collected between 2018 to 2019) using a binary logistic regression from UKHLS with a mean age of 47.01 (S.D. = 16.31) years old with 42.62% males. Results: The current study found that Openness (OR = 0.68, p < 0.01, 95% C.I. (0.51, 0.89)) and Conscientiousness (OR = 0.70, p < 0.05, 95% C.I. (0.52, 0.93)) are positively associated with a reduced risk of MS diagnosis in 7 years. Conclusion: Health professionals can use findings from the current study as evidence for developing tools for assessing the risk of MS, and providing interventions for people who may be at high risk of MS based on their personality traits.

Genotyping of ARNTL and CLOCK Circadian Rhythm Gene Polymorphisms in Iranian Patients with Multiple Sclerosis

Background: Multiple sclerosis (MS) is a central nervous system disease accompanied by variable symptoms such as optic neuritis, fatigue, spasticity, neuro-urological dysfunction, paresthesia, and headache. The frequency of MS was reported differently in geographical latitude, which may be in relation to genetic changes in circadian rhythm regulator genes, including aryl hydrocarbon receptor nuclear translocator-like (ARNTL) and circadian locomotor output cycles kaput (CLOCK). Objectives: This study aimed at genotyping rs3789327 in the ARNTL and rs6811520 in the CLOCK genes and their association with MS in the Iranian population. Methods: Totally, 100 patients with relapsing-remitting multiple sclerosis (RRMS) and 100 healthy controls were recruited. DNA extracted from the whole blood of all patients was genotyped by high-resolution melting (HRM) real-time PCR method for the rs3789327 and rs6811520 within the ARNTL and CLOCK genes, respectively, then the HRM results were confirmed by Sanger sequencing method. Results: Our results showed a statistically significant difference in genotype distributions in the CLOCK gene (rs6811520, P = 0.023) in MS and healthy controls, but in the ARNTL gene, there was no significant change in rs3789327 genotypic distribution between MS patients and healthy individuals (P = 0.2). The TC genotype of the rs6811520 was associated with a higher risk for MS [P = 0.006, OR = 4.164, 95% confidence intervals (CI) 1.43 - 12.09]. Conclusions: The present results suggested that genetic variations in the CLOCK gene are a risk factor for MS.

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.

Correlation of -475 IL-2 Promoter Gene Polymorphisms and the Levels of Serum IL-2 on the Risk of Multiple Sclerosis.

The aim of present study is to asset the IL-2 promoter gene (SNP -475) as a candidate gene for multiple sclerosis (MS) susceptibility. This study included 70 patients with relapsing - remitting multiple sclerosis (RRMS) and 50 healthy controls. Following the extraction of genomic DNA from peripheral blood, frequency of genotypes and alleles of SNP -475 was calculated using Restriction fragment length polymorphism-polymer chain reaction (RFLP-PCR) and then the results were analyzed statistically. The results revealed the unusual ratio for the heterozygous (AT) was 1.6972 indicating that heterozygous patients were at higher risk of multiple sclerosis than wild homozygous (AA), and homomutant (TT). The results show protective role for - 475 IL-2 promoter among individuals with multiple sclerosis, (O.R: 0.4872; C.I. 95%: 0.1617- 1.4680) and (O.R: 0.9275; C.I. 95%: 0.2476 - 3.4745) for both AA and TT genotypes, respectively. Our results showed that in this population of Iraqi patients, the AT genotype / A allele of -475 IL-2 promoter gene SNP may include attributed factors for MS predisposition.

Vitamin D related genetic polymorphisms affect serological response to high-dose vitamin D supplementation in multiple sclerosis

A poor 25-hydroxyvitamin D (25(OH)D) status is a much replicated risk factor for developing multiple sclerosis (MS), and several vitamin D-associated single nucleotide polymorphisms (SNPs) have been associated with a higher risk of MS. However, studies on the benefit of vitamin D supplementation in MS show inconclusive results. Here, we explore whether vitamin D-associated SNPs and MS risk alleles confound serological response to vitamin D supplementation. 34 participants from the SOLARIUM study consented to genotyping, of which 26 had vitamin D data available. The SOLARIUM study randomised relapsing-remitting MS patients to placebo or 14,000 IU vitamin D3 for 48 weeks. Participants were categorised as either 'carriers' or 'non-carriers' of the risk allele for 4 SNPs: two related to D binding protein (DBP) and associated with lower 25(OH)D levels (rs4588 and rs7041), and two related to vitamin D metabolism enzymes CYP27B1 and CYP24A1 and associated with a higher risk of MS (rs12368653; rs2248359, respectively). 25(OH)D levels were determined at baseline and after 48 weeks. The DBP-related SNPs showed no difference in 25(OH)D status at baseline, but carriers of the rs7041 risk allele showed lower 25(OH)D-levels compared to non-carriers after 48 weeks of supplementation (median 224.2 vs. 332.0 nmol/L, p = 0.013). For CYP related SNPs, neither showed a difference at baseline, but carriers of the rs12368653 risk allele showed higher 25(OH)D-levels compared to non-carriers after 48 weeks of supplementation (median 304.1 vs. 152.0 nmol/L, p = 0.014). Vitamin D-related SNPs affect the serological response to high-dose vitamin D supplementation. The effects on more common doses of vitamin D, as well as the clinical consequence of this altered response, need to be investigated further.

Genetic, Environmental and Lifestyle Determinants of Accelerated Telomere Attrition as Contributors to Risk and Severity of Multiple Sclerosis.

Telomeres are protective structures at the ends of linear chromosomes. Shortened telomere lengths (TL) are an indicator of premature biological aging and have been associated with a wide spectrum of disorders, including multiple sclerosis (MS). MS is a chronic inflammatory, demyelinating and neurodegenerative disease of the central nervous system. The exact cause of MS is still unclear. Here, we provide an overview of genetic, environmental and lifestyle factors that have been described to influence TL and to contribute to susceptibility to MS and possibly disease severity. We show that several early-life factors are linked to both reduced TL and higher risk of MS, e.g., adolescent obesity, lack of physical activity, smoking and vitamin D deficiency. This suggests that the mechanisms underlying the disease are connected to cellular aging and senescence promoted by increased inflammation and oxidative stress. Additional prospective research is needed to clearly define the extent to which lifestyle changes can slow down disease progression and prevent accelerated telomere loss in individual patients. It is also important to further elucidate the interactions between shared determinants of TL and MS. In future, cell type-specific studies and advanced TL measurement methods could help to better understand how telomeres may be causally involved in disease processes and to uncover novel opportunities for improved biomarkers and therapeutic interventions in MS.

Multiple sclerosis projection in Tehran, Iran using Bayesian structural time series

BackgroundThe prevalence of Multiple Sclerosis (MS) has been increasing worldwide and the highest prevalence ratio among Asian countries was reported in Iran. This study aims to estimate the increase in MS occurrence during more than three decades in Tehran and forecast the future condition of the disease using time series approaches for the next ten years.MethodsThe cross-sectional study was conducted from 1999 to 2019 based on records of MS cases from Iranian MS Society (IMSS) registry system. The prevalence was estimated using population data presented by the Statistical Centre of Iran. Through Bayesian Structural Time Series (BSTS) model, we want to predict the prevalence of familial and sporadic MS in the next ten years. .ResultsAmong 22,421 cases with MS, 16,831 (75.1 %) were female and 5589 (24.9 %) were male. Female to male ratio was 3.0:1 and the number of familial MS cases were 2982 (13.3 %) of subjects. Female gender was less responsible for higher rate of MS in familial definition (beta = 0.020) in comparison to sporadic cases (beta = 0.034). Forecasting by BSTS revealed an increase in MS prevalence for the next ten years so that the prevalence rate for total, familial and sporadic MS respectively begins with 189.50 (183.94-195.14), 25.69 (24.97–26.45) and 163.74(159.06-168.57) in 2020 and ends with 220.84 (171.48-266.92), 30.79 (24.16–37.15), and 189.33(146.97-230.19) in 2029.ConclusionsAccording to the findings, MS prevalence increased during three decades and it will increase over the next ten years. Tehran province is one of the regions with highest MS prevalence in Asia. The results of present study indicated that females are at higher risk for MS than males in both sporadic and familial MS.

Association between polymorphisms in the vitamin D receptor and susceptibility to multiple sclerosis.

Multiple sclerosis (MS) is a neurodegenerative chronic inflammatory. Mutations in the vitamin D receptor (VDR) gene can substantially affect serum vitamin D levels or alter its functionality, and can consequently increase susceptibility to developing MS. The objective of this study was to evaluate the association between polymorphisms in the VDR gene and risk of MS in a (Spanish) Caucasian population. We conducted a retrospective case-control study comprising 209 patients with relapsing-remitting multiple sclerosis (RRMS) and 836 controls of Caucasian origin from southern Spain. The ApaI (rs7975232), BsmI (rs1544410), Cdx2 (rs11568820), FokI (rs2228570), and TaqI (rs731236) gene polymorphisms were determined by allelic discrimination real-time PCR using TaqMan probes. The recessive logical regression model, adjusted for age and sex, revealed that the TT genotype for VDR FokI (rs2228570) polymorphism was associated with higher risk of MS (P = 0.0150; OR = 1.82; 95% CI = 1.12-2.94; TT vs. CT + CC). No association between the other polymorphisms and development of MS was found in any of the models analyzed. The haplotype analysis, adjusted for age, smoking, and sex, did not find any statistically significant association between the haplotypes analyzed and risk of MS. The VDR FokI (rs2228570) polymorphism was significantly associated with developing MS. We found no influence of the ApaI (rs7975232), BsmI (rs1544410), Cdx2 (rs11568820), FokI (rs2228570), and TaqI (rs731236) gene polymorphisms on the risk of developing MS in our patients.

Skin Phototype Could Be a Risk Factor for Multiple Sclerosis.

Environmental and genetic factors are assumed to be necessary for the development of multiple sclerosis (MS), however its interactions are still unclear. For this reason here, we have not only analyzed the impact on increased risk of MS of the best known factors (HLA-DRB1*15:01 allele, sun exposure, vitamin D levels, smoking habit), but we have included another factor (skin phototype) that has not been analyzed in depth until now. This study included 149 MS patients and 147 controls. A multivariate logistic regression (LR) model was carried out to determine the impact of each of the factors on the increased risk of MS. Receiver Operating Characteristics (ROC) analysis was performed to evaluate predictive value of the models. Our multifactorial LR model of susceptibility showed that females with light brown skin (LBS), smokers and who had HLA-DRB1*15:01 allele had a higher MS risk (LBS: OR = 5.90, IC95% = 2.39–15.45; smoker: OR = 4.52, IC95% = 2.69–7.72; presence of HLA-DRB1*15:01: OR = 2.39, IC95% = 1.30–4.50; female: OR = 1.88, IC95% = 1.08–3.30). This model had an acceptable discriminant value with an Area Under a Curve AUC of 0.76 (0.69–0.82). Our study indicates that MS risk is determined by complex interactions between sex, environmental factors, and genotype where the milieu could provide the enabling proinflammatory environment that drives an autoimmune attack against myelin by self-reactive lymphocytes.

Differences by Sex in the Workup of Children at High Risk for Multiple Sclerosis (1917)

Differences by Sex in the Workup of Children at High Risk for Multiple Sclerosis (1917)

Differential Expression of HERV-W in Peripheral Blood in Multiple Sclerosis and Healthy Patients in Two Different Ethnic Groups.

Overexpression of the Human endogenous retrovirus W (HERV-W) group of inherited retroviruses has been consistently linked with Multiple Sclerosis (MS). However most of the studies on this link have focused on European genetic groups with a very high risk of MS and it is not clear that this relationship holds for all ethnic groups. This study examined via qPCR the RNA expression in peripheral blood of HERV-W (the multiple sclerosis associated retrovirus variant MSRV) of MS patients and healthy controls from two ethnic groups with very different risk rates of MS. Population one was derived from the UK with a Northern European genetic background and an MS risk rate of 108/100,000, population two was derived from the republic of Tatarstan, Russian Federation, with a mixed Russian (Eastern European) and Tartar (Turkic or Volga/Urals) population with an MS risk rate of 21-31/100,000. The Russian population displayed a significantly higher basal level of expression of MSRV in both healthy and MS individuals when compared to the British control population with a trend in the Russian population towards higher expression levels in MS patients than healthy patients.

Bilateral optic perineuritis: A case report

Optic perineuritis (OPN) is a rare form of orbital inflammation which affects the optic nerve sheath. Clinical manifestations commonly include subacute visual loss, retro-orbital pain exacerbated by ocular movement, and disc edema. Diagnosis is based on the clinical and radiological features of the patient. We present the case of a 18 year old male of good health admitted to our department due to bilateral visual loss. A week before his admission he experienced a progressive reduction in visual acuity, first right-sided and then bilateral. One day before admission he had scotomas bilaterally and reported pain during eye movements. The visual field exam confirmed the reduced acuity, and the fundus examination showed optic disc edema. Blood and CSF tests for infections, including VDRL, were negative. Tests of the CSF were also normal. No oligoclonal bands were detected in the CSF. Tests for connective tissue diseases were negative. An orbital MRI scan was performed, showing an increased signal intensity around both optic nerves. Although most cases of OPN are isolated and idiopathic, there have been reports of cases caused by infectious or other inflammatory diseases, such as Wegener’s granulomatosis, Crohn disease, sarcoidosis, syphilis etc. In OPN, the MRI scans demonstrate signal enhancement around the optic nerves. The treatment of choice is corticosteroids. The differentiation between OPN and optic neuritis (ON) is necessary, because both diseases have similar clinical features. Patients with ON show a more rapid progression, they are usually young adults and they also demonstrate a high risk of multiple sclerosis.