Low Prevalence Of Multiple Sclerosis Research Articles

Multiple sclerosis care in Pakistan; analysis of data presented at first PAKTRIMS conference

Novel data on Multiple Sclerosis (MS) in Pakistan from leading institutes in the country was presented at the first Pakistan Treatment in Multiple Sclerosis (PAKTRIMS) Conference, organized by the section of neurology, department of medicine, Aga Khan University, Karachi on Saturday, December 18, 2021. Pakistan has been considered to have a low prevalence of MS; however, recent research reveals that it is not as uncommon as previously believed to be in the country. The true prevalence and incidence of MS in the country is unknown because of dearth of research. Data of MS patients enrolled in various private and public institutes in Pakistan highlights the current treatment offered in Pakistan for MS patients with steroids as the mainstay treatment and disease modifying drugs (DMD) mainly including azathioprine, ocrelizumab and rituximab. Available data featuring disease progression indicates a successful response to the treatment offered to patients with improved expanded disability status scale (EDSS) and radiological findings. The conference was a steppingstone towards future research in MS in Pakistan as it highlighted what is furthered required to have a better picture of the disease in the country. Available data majorly outlines demographic characteristics and disease characteristics, however, there is a need for research to fill in the gap for data in reporting MS diagnosis, treatment, and disease outcome to develop a better healthcare system geared towards MS patients in a low- and middle-income Country (LMIC)

CPT1A plays a key role in the development and treatment of multiple sclerosis and experimental autoimmune encephalomyelitis

Human mutations in carnitine palmitoyl transferase 1A (CPT1A) are correlated with a remarkably low prevalence of multiple sclerosis (MS) in Inuits (P479L) and Hutterites (G710E). To elucidate the role of CPT1A, we established a Cpt1a P479L mouse strain and evaluated its sensitivity to experimental autoimmune encephalomyelitis (EAE) induction. Since CPT1a is a key molecule in lipid metabolism, we compared the effects of a high-fat diet (HFD) and normal diet (ND) on disease progression. The disease severity increased significantly in WT mice compared to that in Cpt1 P479L mice. In addition, WT mice receiving HFD showed markedly exacerbated disease course when compared either with Cpt1a P479L mice receiving HFD or WT control group receiving ND. Induction of EAE caused a significant decrease of myelin basic protein expression in the hindbrain of disease affected WT mice in comparison to Cpt1a P479L mice. Further, WT mice showed increased expression of oxidative stress markers like Nox2 and Ho-1, whereas expression of mitochondrial antioxidants regulator Pgc1α was increased in Cpt1a P479L mice. Our results suggest that, lipids metabolism play an important role in EAE, as shown by the higher severity of disease progression in both WT EAE and WT EAF HFD-fed mice in contrast to their counterpart Cpt1a P479L mutant mice. Interestingly, mice with downregulated lipid metabolism due to the Cpt1a P479L mutation showed resistance to EAE induction. These findings support a key role for CPT1A in the development of EAE and could be a promising target in MS treatment.

Lower prevalence of multiple sclerosis in First Nations Canadians.

We compared the incidence and prevalence of multiple sclerosis (MS) between First Nations (FN) and non-FN populations in Manitoba. We applied previously validated algorithms to population-based administrative (health claims) data from Manitoba, Canada, to identify all persons with MS from 1984 to 2011. We identified FN individuals using the Municipality of Registration field held at Manitoba Health. We compared the incidence and prevalence of MS between the FN and non-FN populations using negative binomial models. From 1984 to 2011, 5,738 persons had MS, of whom 64 (1.1%) were of FN ethnicity. The average annual incidence rate per 100,000 population was 8.15 (95% confidence interval [CI] 5.98-11.1) in the FN population and 15.7 (95% CI 15.1-16.3) in the non-FN population (incidence rate ratio 0.52; 95% CI 0.38-0.71). In 1984, the crude prevalence of MS per 100,000 population was 35.8 (95% CI 14.9-86.1) in the FN population and 113.3 (95% CI 106.3-120.8) in the non-FN population. Between 1984 and 2011, the age-standardized prevalence of MS increased by 351% to 188.5 (95% CI 146.6-230.4) in the FN population. In contrast, the prevalence of MS per 100,000 general population increased by 225%-418.4% (95% CI 405.8-431.0). The incidence and prevalence of MS are twofold lower in the FN population than the non-FN population. Nonetheless, the prevalence of MS in FN Manitobans is higher than in other indigenous populations outside Canada. Given reports of more rapid disability progression among FN Canadians with MS, and the rising prevalence of MS in this population, attention should be directed to the needs of this population.

Prevalence, treatments and medical cost of multiple sclerosis in Japan based on analysis of a health insurance claims database.

ObjectiveTo understand, through an analysis of health insurance claims data, the current treatment status and medical cost of multiple sclerosis (MS) in Japan.MethodsWe analyzed claims data (January 2005–January 2016) from the Japan Medical Data Center Co., Ltd., identifying MS patients, except those with neuromyelitis optica, using an algorithm based on diagnosis codes. Prescription drug usage and medical costs for MS patients were analyzed.ResultsA total of 713 MS patients were identified in the database. Between 2011 and 2015, the age‐adjusted prevalence of MS in the database increased from 0.015% to 0.019%, and the female‐to‐male ratio increased from 1.70 to 2.03. The prescription rate for disease‐modifying therapy drugs was higher in larger care settings. Prescriptions for fingolimod increased from 2011, with a concomitant decrease in prescriptions for interferon. The per patient per month cost for MS was ¥124 337 (US$1190 or €1084, as of October 2016). This was higher than the costs for Parkinson's disease (¥84 410), myasthenia gravis (¥82 944) and rheumatoid arthritis (¥53 843). However, the total per member per month cost for MS, which represents the population‐based economic impact, was ¥25.2, which was lower than the parallel costs for Parkinson's disease (¥123.0) and rheumatoid arthritis (¥311.6) because of the low prevalence of MS in Japan.ConclusionsUsing real‐world data, we obtained up‐to‐date prevalence, treatment status and medical cost information for MS in Japan. The present results showed the efficacy of a real‐world database to obtain the latest national trends for rare diseases, such as MS; this could have important implications for clinicians and policymakers.

Multiple Sclerosis in Latin Americans: Genetic Aspects.

Latin Americans (LA) are a heterogeneous, multiethnic group of individuals who inhabit the continental countries in Latin America (LATAM), Caribbean islands and constitute the largest ethnic minority in the USA. Commonly used terminology and ethno racial classifications to define these groups may not be accurate. Risk for multiple sclerosis (MS) among LA is generally low to medium but frequencies are increasing in the American hemisphere. Genome-Wide Association Studies (GWAS) in LA show diverse variants and genetic proportions among Mestizos, the most representative ethnic population, who themselves are the product of centuries of interracial mixing between Native Americans (or Amerindians), White Caucasian Europeans, and Black Africans. Genetic distribution diversity appears to be related to migratory and historical and socio-political factors in LATAM. Epidemiologic studies show an extremely low prevalence of MS among non-mixed Amerindians; this has been attributed to protective ancestral Asian genetics and possibly, environmental factors. Mestizos and biracial LA of African ancestry have more susceptibility to MS apparently due to the historical introduction of the European HLA-DRB1*1501 gene. Contribution from HLA typing, GWAS, and ancestry informative markers (AIMs) has been determinant in the current LA genetic understanding but more regional studies are needed. The relationship between genetics and disease regional distribution is emphasized.

Temperature dependence of multiple sclerosis mortality rates in the United States

Background: It is well known that multiple sclerosis (MS) patients are very sensitive to heat events. However, how MS patients respond to the significant temperature difference between the high- and low-latitude regions is not understood. Objective: The goal is to identify the primary factor responsible for the fact that MS mortality rates of the United States is more than three times higher in the northern states than in the southern states. Methods: Correlation coefficients between the age-adjusted mortality rate of MS as the underlying cause of death and the state average temperature, altitude, latitude, duration of sunshine hours, and solar radiation in the 48 contiguous states were compared. Results: MS mortality rates correlate significantly and inversely with temperatures in the 48 states (correlation coefficient r = −0.812 and significance p = 0.00). Durations of sunshine hours and solar radiation do not correlate significantly with MS mortality rates (r = −0.245, −0.14, and p = 0.101, 0.342, respectively). Conclusion: High environmental temperature is the primary reason for the low MS mortality rates and likely the low MS prevalence in low-latitude regions. Implication of the study result is that benefits of long-term heat acclimation through gradual and prolonged exposure to environmental heat for MS patients may be greatly underappreciated.

An essential role of virus-infected B cells in the marmoset experimental autoimmune encephalomyelitis model.

Infection with Epstein–Barr virus (EBV) has been associated with an enhanced risk of genetically susceptible individuals to develop multiple sclerosis (MS). However, an explanation for the contrast between the high EBV infection prevalence (60–90%) and the low MS prevalence (0.1%) eludes us. Here we propose a new concept for the EBV–MS association developed in the experimental autoimmune encephalomyelitis model in marmoset monkeys, which are naturally infected with the EBV-related γ1-herpesvirus CalHV3. The data indicate that the infection of B cells with a γ1-herpesvirus endows them with the capacity to activate auto-aggressive CD8+ T cells specific for myelin oligodendrocyte glycoprotein.

HLA-DRB1*14 is a protective allele for multiple sclerosis in an admixed Colombian population.

Objective:The aim of this study was to determine ancestry informative markers, mitochondrial DNA haplogroups, and the association between HLA-DRB1 alleles and multiple sclerosis (MS) in a group of patients from Bogotá, Colombia.Methods:In this case-control study, genomic DNA was isolated and purified from blood samples. HLA-DRB1 allele genotyping was done using PCR. Mitochondrial hypervariable region 1 was amplified and haplogroups were determined using HaploGrep software. Genomic ancestry was estimated by genotyping a panel of ancestry informative markers. To test the association of HLA polymorphisms and MS, we ran separate multivariate logistic regression models. Bonferroni correction was used to account for multiple regression tests.Results:A total of 100 patients with MS (mean age 40.4 ± 12 years; 70% females) and 200 healthy controls (mean age 37.6 ± 11 years; 83.5% females) were included in the analysis. Ancestry proportions and haplogroup frequencies did not differ between patients and controls. HLA-DRB1*15 was present in 31% of cases and 13.5% of controls, whereas HLA-DRB1*14 was present in 5% of cases and 15.5% of controls. In the multivariate model, HLA-DRB1*15 was significantly associated with MS (odds ratio [OR] = 3.05, p < 0.001), whereas HLA-DRB1*14 was confirmed as a protective factor in our population (OR = 0.16, p = 0.001).Conclusions:This study provides evidence indicating that HLA-DRB1*15 allele confers susceptibility to MS and HLA-DRB1*14 allele exerts resistance to MS in a highly admixed population. This latter finding could partially explain the low prevalence of MS in Bogotá, Colombia.

Estimated Prevalence and Incidence of Multiple Sclerosis in Iran

Background: Multiple Sclerosis (MS) is a chronic demyelinating disease of the central nervous system and its epidemiology has changed in recent years. Previously, Iran was considered to have a low MS prevalence. In this study, we aimed to update the prevalence and incidence of MS in Iran. Patients and Methods: This study was conducted based on the data derived from the new report of Iran's Ministry Of Health and Medical Education (MOHME) regarding the patients who have registered to obtain support for treatment in Iran till the end of 2013. Results: Among the 42,200 registered patients, 32,477 were female and 9,723 were male (sex ratio: 3.34: 1), and 4,545 were diagnosed in 2013. This resulted in a prevalence of 54.51 and an incidence of 5.87 per 100,000. Conclusion: According to our study results, Iran has a medium-to-high prevalence rate of MS. According to the previous epidemiologic studies from Iran, it seems that the prevalence of MS significantly has increased during recent years. This rate is similar to what is seen in many western countries.

The Refinement of Genetic Predictors of Multiple Sclerosis

A recent genome wide association study (GWAS) demonstrated that more than 100 genetic variants influence the risk of multiple sclerosis (MS). We investigated what proportion of the general population can be considered at high genetic risk of MS, whether genetic information can be used to predict disease development and how the recently found genetic associations have influenced these estimates. We used summary statistics from GWAS in MS to estimate the distribution of risk within a large simulated general population. We profiled MS associated loci in 70 MS patients and 79 healthy controls (HC) and assessed their position within the distribution of risk in the simulated population. The predictive performance of a weighted genetic risk score (wGRS) on disease status was investigated using receiver operating characteristic statistics. When all known variants were considered, 40.8% of the general population was predicted to be at reduced risk, 49% at average, 6.9% at elevated and 3.3% at high risk of MS. Fifty percent of MS patients were at either reduced or average risk of disease. However, they showed a significantly higher wGRS than HC (median 13.47 vs 12.46, p = 4.08×10−10). The predictive performance of the model including all currently known MS associations (area under the curve = 79.7%, 95%CI = 72.4%–87.0%) was higher than that of models considering previously known associations. Despite this, considering the relatively low prevalence of MS, the positive predictive value was below 1%. The increasing number of known associated genetic variants is improving our ability to predict the development of MS. This is still unlikely to be clinically useful but a more complete understanding of the complexity underlying MS aetiology and the inclusion of environmental risk factors will aid future attempts of disease prediction.

Modest familial risks for multiple sclerosis: a registry-based study of the population of Sweden

Data on familial recurrence rates of complex diseases such as multiple sclerosis give important hints to aetiological factors such as the importance of genes and environment. By linking national registries, we sought to avoid common limitations of clinic-based studies such as low numbers, poor representation of the population and selection bias. Through the Swedish Multiple Sclerosis Registry and a nationwide hospital registry, a total of 28 396 patients with multiple sclerosis were identified. We used the national Multi-Generation Registry to identify first and second degree relatives as well as cousins, and the Swedish Twin Registry to identify twins of patients with multiple sclerosis. Crude and age corrected familial risks were estimated for cases and found to be in the same range as previously published figures. Matched population-based controls were used to calculate relative risks, revealing lower estimates of familial multiple sclerosis risks than previously reported, with a sibling recurrence risk (λs = 7.1; 95% confidence interval: 6.42-7.86). Surprisingly, despite a well-established lower prevalence of multiple sclerosis amongst males, the relative risks were equal among maternal and paternal relations. A previously reported increased risk in maternal relations could thus not be replicated. An observed higher transmission rate from fathers to sons compared with mothers to sons suggested a higher transmission to offspring from the less prevalent sex; therefore, presence of the so-called 'Carter effect' could not be excluded. We estimated the heritability of multiple sclerosis using 74 757 twin pairs with known zygosity, of which 315 were affected with multiple sclerosis, and added information from 2.5 million sibling pairs to increase power. The heritability was estimated to be 0.64 (0.36-0.76), whereas the shared environmental component was estimated to be 0.01 (0.00-0.18). In summary, whereas multiple sclerosis is to a great extent an inherited trait, the familial relative risks may be lower than usually reported.

Management of optic neuritis

Optic neuritis is an inflammatory condition of the optic nerve characterized by a sudden onset of unilateral visual loss, usually affecting young females. Demyelination associated with multiple sclerosis (MS) is the most common cause in regions where MS is prevalent; while in other places, there are a substantial proportion of cases where infective or autoimmune causes are seen. Optic Neuritis Treatment Trial (ONTT) was the first major study that provided information on the natural history, role of steroids in treatment and risk of development of MS. Subsequently, numerous clinical trials have evaluated different modalities of management of optic neuritis and MS. The Controlled High-Risk Subjects Avonex Multiple Sclerosis Prevention Study (CHAMPS); the Prevention of Relapses and Disability by Interferon β-1a Subcutaneously in Multiple Sclerosis (PRISMS) Trial; and, most recently, the Betaferon in Newly Emerging Multiple Sclerosis for Initial Treatment (BENEFIT) Study have provided large amount of information on the natural history of optic neuritis and management options available. However, due to the low prevalence of MS reported in Asian studies, high cost of therapy and indefinite time period of treatment, it may not be cost effective to start interferon therapy in most cases.

Geographic variations of multiple sclerosis in France

France is located in an area with a medium to high prevalence of multiple sclerosis, where its epidemiology is not well known. We estimated the national and regional prevalence of multiple sclerosis in France on 31 October 2004 and the incidence between 31 October 2003 and 31 October 2004 based on data from the main French health insurance system: the Caisse Nationale d'Assurance Maladie des Travailleurs Salariés. The Caisse Nationale d'Assurance Maladie des Travailleurs Salariés insures 87% of the French population. We analysed geographic variations in the prevalence and incidence of multiple sclerosis in France using the Bayesian approach. On the 31 October 2004, 49 417 people were registered with multiple sclerosis out of the 52 359 912 insured with the Caisse Nationale d'Assurance Maladie des Travailleurs Salariés. Among these, 4497 were new multiple sclerosis cases declared between 31 October 2003 and 31 October 2004. After standardization for age, total multiple sclerosis prevalence in France was 94.7 per 100,000 (94.3-95.1); 130.5 (129.8-131.2) in females and 54.8 (54.4-55.3) in males. The national incidence of multiple sclerosis between 31 October 2003 and 31 October 2004 was 7.5 per 100,000 (7.3-7.6); 10.4 (10.2-10.6) in females and 4.2 (4.0-4.3) in males. The prevalence and incidence of multiple sclerosis were higher in North-Eastern France, but there was no obvious North-South gradient. This study is the first performed among a representative population of France (87%) using the same method throughout. The Bayesian approach, which takes into account spatial heterogeneity among geographical units and spatial autocorrelation, did not confirm the existence of a prevalence gradient but only a higher prevalence of multiple sclerosis in North-Eastern France and a lower prevalence of multiple sclerosis in the Paris area and on the Mediterranean coast.

Amelioration of experimental autoimmune encephalitis by novel peptides: Involvement of T regulatory cells

The purpose of the present study was to develop a peptide for treatment of multiple sclerosis (MS). We have tested the effect of a novel anti-inflammatory peptide (KGHYAERVG, termed IIIM1) on experimental autoimmune encephalitis (EAE), an animal model of MS. Our findings demonstrate significant reduction in neurological score following oral administration of IIIM1. Structural studies revealed that the entire peptide is required for activity. The peptide caused significant reduction in IL17, interferon γ, IL23 and IL12 production by isolated splenocytes and concomitant elevation of anti-inflammatory cytokines. IIIM1 elevated T regulatory cells (Tregs, CD4 +CD25 +FoxP3 +) in brain and spleen of EAE mice. Similar proliferative effect was observed in isolated human and mouse Tregs in vitro. Stimulation of Tregs by IIIM1 caused production of a new peptide termed RA1 present in Oryza Sativa Japonica group. This Japanese rice peptide ameliorated neurological symptoms in the EAE model. Similar beneficial effect was observed upon oral administration of an extract of Japanese rice. In conclusion, oral treatment with IIIM1 ameliorates EAE symptoms via stimulation of Tregs to proliferate and produce RA1 which reduces EAE symptoms. RA1 might be involved in the relatively low prevalence of MS in Japan and other Japanese rice-eating populations.

The link between multiple sclerosis, T regulatory cells and Japanese rice (96.1)

Abstract The purpose of the present study was to develop a peptide for treatment of multiple sclerosis (MS). We have tested the effect of a novel antiinflammatory peptide (KGHYAERVG, termed IIIM1) on experimental autoimmune encephalitis (EAE), an animal model of MS. Our findings demonstrate significant reduction in neurological score following oral administration of IIIM1, as compared to the control groups received the vehicle (saline). Structural studies revealed that the entire peptide is required for activity. The peptide caused significant reduction in IL17, interferon gamma and IL12 production by isolated splenocytes and concomitant elevation of antiinflammatory cytokines. IIIM1 elevated T regulatory cells (Tregs, CD4+CD25+FoxP3+) in brain and spleen of EAE mice. Similar proliferative effect was observed in isolated human and mouse Tregs in vitro. Stimulation of Tregs by IIIM1 caused production of a new peptide termed RA1 present in Oryza Sativa Japonica group. This Japanese rice peptide ameliorated neurological symptoms in the EAE model. Similar beneficial effect was observed upon oral administration of an extract of Japanese rice. In conclusion, oral treatment with IIIM1 ameliorates EAE symptoms via stimulation of Tregs to proliferate and produce RA1 which reduces EAE symptoms. These findings may explain the relatively low prevalence of MS in Japan and other Japanese rice-eating populations. (This work was supported in part by The Israel Science Foundation grant 747/05).

Evaluation of multiple sclerosis diagnostic criteria in Suzhou, China – risk of under-diagnosis in a low prevalence area

To evaluate the discharge diagnosis of demyelinating diseases in the central nervous system (CNS) and analyze the predictive value of the new diagnostic criteria in Suzhou, China. We collected clinical information and data of laboratory examinations for all cases with a diagnosis of various demyelinating diseases in the CNS. All data were reviewed individually by four senior neurologists, and a diagnosis was finally given to each patient according to the McDonald criteria and the Poser criteria for multiple sclerosis (MS). In the analysis, 176 patients with a diagnosis of demyelinating diseases in the CNS at discharge were included. In 82 patients with a diagnosis of MS at discharge, the MS diagnosis was confirmed for 74 patients according to the McDonald criteria for MS, and the positive predictive value for the discharge diagnosis of MS was 90.2% (74/82). According to the Poser criteria, 61 patients were diagnosed as MS. The consistency of the two diagnostic criteria for MS was 78.4%, based on the results of the evaluation. Under-diagnosis of MS could be one of the explanations for the low prevalence of MS in China. Compared to the Poser criteria, the McDonald criteria had a higher sensitivity for the diagnosis of MS.

Association of the HLA-DRB1 ⁎15 allele group and the DRB1 ⁎1501 and DRB1 ⁎1503 alleles with multiple sclerosis in White and Mulatto samples from Brazil

Multiple sclerosis (MS) is a multifactorial inflammatory disease that primarily affects the central nervous system. Genes and environmental factors probably interact in MS susceptibility and outcome; however, their roles have not been elucidated yet. The evaluation of the HLA-DRB1 gene in the Brazilian population is of particular interest in evidencing the behavior of HLA-DRB1 alleles in a highly admixed population inserted in an environment of low MS prevalence. The present results suggest that a given HLA-DRB1 allele may exhibit different behaviors, i.e. confer resistance or susceptibility, in response to the environmental and/or genetic (ethnic) backgrounds that characterize a sampled population.

Environmental risk factors for multiple sclerosis. Part I: The role of infection

Although genetic susceptibility explains the clustering of multiple sclerosis (MS) cases within families and the sharp decline in risk with increasing genetic distance, it cannot fully explain the geographic variations in MS frequency and the changes in risk that occur with migration. Epidemiological data provide some support for the "hygiene hypothesis," but with the additional proviso for a key role of Epstein-Barr virus (EBV) in determining MS risk. We show that whereas EBV stands out as the only infectious agent that can explain many of the key features of MS epidemiology, by itself the link between EBV and MS cannot explain the decline in risk among migrants from high to low MS prevalence areas. This decline implies that either EBV strains in low-risk areas have less propensity to cause MS, or that other infectious or noninfectious factors modify the host response to EBV or otherwise contribute to determine MS risk. The role of infectious factors is discussed here; in a companion article, we will examine the possible role of noninfectious factors and provide evidence that high levels of vitamin D may have a protective role, particularly during adolescence. The primary purpose of these reviews is to identify clues to the causes of MS and to evaluate the possibility of primary prevention.

Low frequency of the disease‐associated DRB1*15‐DQB1*06 haplotype may contribute to the low prevalence of multiple sclerosis in Sami

This study confirms a low frequency of multiple sclerosis (MS) among Sami. Only 12 Sami with a diagnosis of MS were identified in the Norwegian Sami population, which represents a significantly lower prevalence of MS in Sami (30/10(5)) compared with other Norwegians (73-164/10(5)). The clinical characteristics as well as the results of human leukocyte antigen (HLA)-DRB1 and -DQB1 typing of the Sami MS patients are reported, showing that three (27%) of the Sami MS patients carried the MS-associated HLA-DRB1*15-DQB1*06 haplotype. Interestingly, the DRB1*15-DQB1*06 haplotype had a significantly reduced frequency among Sami controls (0.086) compared with non-Sami Norwegian controls (0.163) (P(corrected) = 0.015). The low frequency of the disease-associated DRB1*15-DQB1*06 haplotype in the Sami population may contribute to the low prevalence of MS in Sami, in addition to other yet unidentified genetic and environmental factors.

The relationship of APOE genetic polymorphism with susceptibility to multiple sclerosis and its clinical phenotypes in Kuwaiti Arab subjects

Background The possible pathogenetic relationship between APOE genetic polymorphism and susceptibility to a variety of neurodegenerative disorders, including multiple sclerosis, is controversial. Previous studies have been conducted in Caucasian subjects, with little or no data on subjects from the Arabian Gulf. We compared the frequencies of specific APOE genotypes and alleles in patients with multiple sclerosis (MS) with frequencies observed in a healthy control Kuwaiti Arab population to relate APOE frequencies with specific identifiable clinical features of the disease. Methods Two groups of subjects were studied: (i) 39 (17 M, 22 F) patients with clinical evidence of MS; (ii) 106 apparently healthy Kuwaitis recruited as control subjects. The MS patients had detailed clinical and laboratory evaluations, and APOE genotypes were determined in all the subjects (patients and controls) by validated PCR methods. Differences in frequencies of APOE alleles and associations of specific alleles with clinical features were assessed. Results There were no significant differences in allele frequencies between patients and controls, although there was a statistically insignificant trend towards lower APOE2 allele frequency in the patients ( p=0.09). There was a significant association of the APOE4 allele with female gender in the patients ( p<0.05). Conclusion In Kuwaitis, a population with low MS prevalence, no statistically significant associations between APOE genetic polymorphism and susceptibility to MS could be established, but there was a trend towards a lower APOE2 frequency with MS and towards increased frequency of APOE4 in female patients and with severe disease.