A Case of Double Standard: Sex Differences in Multiple Sclerosis Risk Factors.
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ABSTRACT:
SUBMITTER: Angeloni B
PROVIDER: S-EPMC8037645 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Multiple sclerosis (MS) is influenced by pregnancy, sex and hormonal factors.A comprehensive understanding of the role of pregnancy, sex and hormonal factors can provide insights into disease mechanisms, and new therapeutic developments and can provide improved patient care and treatment.Based on an international conference of experts and a comprehensive PubMed search for publications on these areas in MS, we provide a review of what is known about the impact of these factors on disease demographics, etiology, pathophysiology and clinical course and outcomes.Recommendations are provided for counseling and management of people with MS before conception, during pregnancy and after delivery. The use of disease-modifying and symptomatic therapies in pregnancy is problematic and such treatments are normally discontinued. Available knowledge about the impact of treatment on the mother, fetus and newborn is discussed. Recommendations for future research to fill knowledge gaps and clarify inconsistencies in available data are made.
| S-EPMC5458871 | biostudies-other
Project description:Background:Several studies have addressed the environmental risk factors for multiple sclerosis (MS). Concerning contradictory results and change of epidemiologic patterns and the role of environmental factors, in the present study, some risk factors, especially environmental factors, on MS were studied. Materials and Methods:This was a retrospective case-control study conducted among 120 patients with MS and 360 healthy individuals in Kerman, Iran. Inclusion criteria included (1) MS disease, diagnosed by a neurologist according to the McDonald criteria, and (2) tendency to participation in the study. Exclusion criteria included (1) suffering from cognitive disorders; (2) incomplete questionnaire; and (3) continuous migration. Data were collected using a questionnaire consisting of personal information and some environmental factors. Data were analyzed using descriptive and inferential statistics. Results:The results showed that diet was associated with a higher risk of MS with the odds ratio (OR) of 14.46 and 95% confidence interval (CI) of 3.02-69.21 (p < 0.001) for vegetarian and OR of 11.74, 95% CI of 4.66-29.57 (p < 0.001) for animal diets. Similarly, vitamin D supplementation contributed to MS risk (OR: 2.27, 95% CI: 1.32-3.89; p < 0.001). In contrast, history of using cow's milk during infancy resulted in a lower risk of MS (OR: 0.33, 95% CI: 0.20-0.52, p < 0.001). Conclusions:This study suggests that different lifestyles including using cow's milk during infancy and avoiding only vegetarian and animal diets may reduce MS risk in southeastern Iran. More studies are suggested to investigate the controversial finding of the negative effect of vitamin D supplementation in this area.
| S-EPMC6178570 | biostudies-other
Project description:Background and objectivesLittle is known of the potential sex and age differences in the MS prodrome. We investigated sex and age differences in healthcare utilization during the MS prodrome.MethodsThis was a population-based matched cohort study linking administrative and clinical data from British Columbia, Canada (population = 5 million). MS cases in the 5 years preceding a first demyelinating event ("administrative cohort;" n = 6,863) or MS symptom onset ("clinical cohort;" n = 966) were compared to age-, sex- and geographically-matched controls (n = 31,865/4,534). Negative binomial and modified Poisson models were used to compare the rates of physician visits and hospitalizations per international classification of diseases chapter, and prescriptions filled per drug class, between MS cases and controls across sex and age-groups (< 30, 30-49, ≥50 years).ResultsIn the administrative cohort, males with MS had a higher relative rate for genitourinary-related visits (males: adjusted Rate Ratio (aRR) = 1.65, females: aRR = 1.19, likelihood ratio test P = 0.02) and antivertigo prescriptions (males: aRR = 4.72, females: aRR = 3.01 P < 0.01). Injury and infection-related hospitalizations were relatively more frequent for ≥50-year-olds (injuries < 30/30-49/≥50: aRR = 1.16/1.39/2.12, P < 0.01; infections 30-49/≥50: aRR = 1.43/2.72, P = 0.03), while sensory-related visits and cardiovascular prescriptions were relatively more common in younger persons (sensory 30-49/≥50: aRR = 1.67/1.45, P = 0.03; cardiovascular < 30/30-49/≥50: aRR = 1.56/1.39/1.18, P < 0.01). General practitioner visits were relatively more frequent in males (males: aRR = 1.63, females: aRR = 1.40, P < 0.01) and ≥50-year-olds (< 30/≥50: aRR = 1.32/1.55, P = 0.02), while differences in ophthalmologist visits were disproportionally larger among younger persons, < 50-years-old (< 30/30-49/≥50: aRR = 2.25/2.20/1.55, P < 0.01). None of the sex and age-related differences in the smaller clinical cohort reached significance (P ≥ 0.05).DiscussionSex and age-specific differences in healthcare use were observed in the 5 years before MS onset. Findings demonstrate fundamental heterogeneity in the MS prodromal presentation.
| S-EPMC9668896 | biostudies-literature
Project description:The pathogenesis of multiple sclerosis (MS) involves complex interactions between genetic susceptibility and environmental triggers. Clinical observations suggest that the study of sex differences might provide important insight into mechanisms of pathogenesis and progression of the disease in patients. MS occurs more frequently in women than in men, indicating that sex-related factors have an effect on an individual's susceptibility to developing the condition. These factors include hormonal, genetic and environmental influences, as well as gene-environment interactions and epigenetic mechanisms. Interestingly, women do not have a poorer prognosis than men with MS despite a higher incidence of the disease and more-robust immune responses, which suggests a mechanism of resilience. Furthermore, the state of pregnancy has a substantial effect on disease activity, characterized by a reduction in relapse rates during the third trimester but an increased relapse rate in the postpartum period. However, pregnancy has little effect on long-term disability in women with MS. The unravelling of the mechanisms underlying these clinical observations in the laboratory and application of the results to the clinical setting is a unique and potentially fruitful strategy to develop novel therapeutic approaches for MS.
| S-EPMC4435786 | biostudies-literature
Project description:BackgroundGenetic and environmental factors seem to have etiologic roles in multiple sclerosis (MS). Kuwait is regarded as medium to high risk country for MS. However, there is a paucity of published data on the risk factors for MS in Kuwait. Therefore, this matched case-control study examined the association between various factors including family history, stressful life events, exposure to tobacco smoke, vaccination history, comorbidities and MS risk in Kuwait.MethodsConfirmed 110 MS cases and age (± 5 years), gender and nationality matched controls (1:1) were enrolled. A pre-tested structured questionnaire was used to collect the data through face-to-face interviews both from cases and controls. Conditional logistic regression was used to analyze the data.ResultsAmong both cases and controls, majority were Kuwaiti (82.7%), and female (76.4%). Multivariable model showed that cases compared to controls were significantly more likely to have had a family history of MS (adjusted matched odds ratio (mORadj) = 5.1; 95% CI: 2.1-12.4; p < 0.001) or less likely to have been vaccinated against influenza A and B viruses before MS onset (mORadj = 0.4; 95% CI: 0.2-0.8; p = 0.010). None of the other variables considered were significantly related to MS status in this study.ConclusionsFamily history of MS had significantly direct, whereas, vaccination against influenza A and B viruses had inverse associations with MS status. Future studies may contemplate to verify the observed results.
| S-EPMC7033919 | biostudies-literature
Project description:Clinically isolated syndrome (CIS) refers to the earliest clinical manifestation of multiple sclerosis (MS). Currently there are no prognostic biological markers that accurately predict conversion of CIS to clinically definite MS (CDMS). Furthermore, the earliest molecular events in MS are still unknown. We used microarrays to study gene expression in naïve CD4+ T cells from 37 CIS patients at time of diagnosis and after one year. Supervised machine-learning methods were used to build predictive models of disease conversion. We identified 975 genes whose expression segregated CIS patients into 4 distinct subgroups. A subset of 108 genes further discriminated patients from one of these (group#1) from other CIS patients. Remarkably, 92% of patients from group #1 converted to CDMS within 9 months. Consistent downregulation of TOB1, a critical regulator of cell proliferation, was characteristic of group #1 patients. Decreased TOB1 expression at the RNA and protein levels was also confirmed in experimental autoimmune encephalomyelitis (EAE). Finally, a genetic association was observed between TOB1 variation and MS progression in an independent cohort. These results indicate that CIS patients at high risk of conversion have impaired regulation of T cell quiescence resulting in earlier activation of pathogenic CD4+ cells. Keywords: Disease state: CIS (Clinically Isolated Syndrome - Multiple Sclerosis) versus control. Time series: some patients and controls were resampled approximately one year later
2008-11-26 | GSE13732 | GEO
Project description:Spontaneous bleeds are a leading cause of death in the pediatric JAG1-related liver disease Alagille syndrome (ALGS). We asked whether there are sex differences in bleeding events in patients, whether Jag1Ndr/Ndr mice display bleeds or vascular defects, and whether discovered vascular pathology can be confirmed in patients non-invasively. We performed a systematic review of patients with ALGS and vascular events following PRISMA guidelines, in the context of patient sex, and found significantly more girls than boys reported with spontaneous intracranial hemorrhage. We investigated vascular development, homeostasis, and bleeding in Jag1Ndr/Ndr mice, using retina as a model. Jag1Ndr/Ndr mice displayed sporadic brain bleeds, a thin skull, tortuous blood vessels, sparse arterial smooth muscle cell coverage in multiple organs, which could be aggravated by hypertension, and sex-specific venous defects. Importantly, we demonstrated that retinographs from patients display similar characteristics with significantly increased vascular tortuosity. In conclusion, there are clinically important sex differences in vascular disease in ALGS, and retinography allows non-invasive vascular analysis in patients. Finally, Jag1Ndr/Ndr mice represent a new model for vascular compromise in ALGS.
| S-SCDT-10_15252-EMMM_202215809 | biostudies-other
Project description:BackgroundStrong evidence supports the role of both genetic and environmental factors in pediatric-onset multiple sclerosis (POMS) etiology.ObjectiveWe comprehensively investigated the association between established major histocompatibility complex (MHC) and non-MHC adult multiple sclerosis (MS)-associated variants and susceptibility to POMS.MethodsCases with onset <18 years (n = 569) and controls (n = 16,251) were included from the United States and Sweden. Adjusted logistic regression and meta-analyses were performed for individual risk variants and a weighted genetic risk score (wGRS) for non-MHC variants. Results were compared to adult MS cases (n = 7588).ResultsHLA-DRB1*15:01 was strongly associated with POMS (odds ratio (OR)meta = 2.95, p < 2.0 × 10-16). Furthermore, 28 of 104 non-MHC variants studied (23%) were associated (p < 0.05); POMS cases carried, on average, a higher burden of these 28 variants compared to adults (ORavg = 1.24 vs 1.13, respectively), though the difference was not significant. The wGRS was strongly associated with POMS (ORmeta = 2.77, 95% confidence interval: 2.33, 3.32, p < 2.0 × 10-16) and higher, on average, when compared to adult cases. Additional class III risk variants in the MHC region associated with POMS were revealed after accounting for HLA-DRB1*15:01 and HLA-A*02.ConclusionPediatric and adult MS share many genetic variants suggesting similar biological processes are present. MHC variants beyond HLA-DRB1*15:01 and HLA-A*02 are also associated with POMS.
| S-EPMC5878964 | biostudies-literature
Project description:Immunological, genetic and environmental factors are believed to play important roles in the pathogenesis of Multiple Sclerosis (MS). There have been many studies on risk factors for MS but these have been mainly in Caucasian populations; robust studies in Arab populations remain relatively uncommon. This study therefore aimed to identify behavioral, socio-cultural, and demographic factors associated with development of MS in Kuwait, a high income Arab country, currently undergoing a demographic transition.In this case- control study, 195 Kuwaiti MS patients and 146 healthy age and sex-matched controls were recruited. Both groups of subjects were interviewed using a structured questionnaire, in relation to anthropometric, socio-cultural and demographic data, residence during the 1990/91 Gulf War and current and past medical history, including medications. We also clinically evaluated, and retrospectively reviewed medical records of patients to derive appropriate clinical information, including associated chronic medical illness requiring long-term treatment.On multiple logistic regression analysis after adjustment for potential confounders including age, gender and BMI, in all the subjects, a positive associations prevail with presence of MS and some sociocultural and demographic factors, which included non-Bedouin ethnicity (AOR 2, 95% CI 1.0-3.9, p 0.049), positive family history of MS (AOR 10.6, 95% CI 3.0-36.9), p < 0.001), and low daily sunlight exposure of < 15min/day (AOR 5.3, 95% CI 2.7-10.5 p < 0.001). In addition, while 41.8% of MS patients indicated at least one comorbidity, only 26.8% of the controls reported any associated physical illness, with the suggestion that presence of certain comorbidities might increase MS risk (AOR 2.4, 95% CI 1.3-4.7, p < 0.001). Other risk variables such as smoking status and mode of routine outdoor dressing were not significant in all the MS subjects taken as a whole, but demonstrated variably positive associations in the MS subgroup classified as those with established disease and those who were newly diagnosed and drug naïve.This study suggests that a positive family history of MS and presence of certain comorbidities appeared to be associated with an increased risk of developing MS. In contrast, relatively increased amount of daily sunlight exposure and Bedouin ethnicity appear to somewhat be protective. It is speculated that the relationship of sunlight exposure with MS might be due to vitamin D availability, and is deserving of further study.
| S-EPMC4488528 | biostudies-other
Project description:To date, scientific research has often focused on one sex, with assumptions that study of the other sex would yield similar results. However, many diseases affect males and females differently. The sex of a patient can affect the risk for both disease susceptibility and progression. Such differences can be brought to the laboratory bench to be investigated, potentially bringing new treatments back to the clinic. This method of research, known as a "bedside to bench to bedside" approach, has been applied to studying sex differences in multiple sclerosis (MS). Females have greater susceptibly to MS, while males have worse disease progression. These two characteristics of the disease are influenced by the immune system and the nervous system, respectively. Thus, sex differences in each system must be studied. Personalized medicine has been at the forefront of research recently, and studying sex differences in disease fits with this initiative. This review will discuss the known sex differences in MS and highlight how investigating them can lead to new insights and potential treatments for both men and women. © 2016 Wiley Periodicals, Inc.
| S-EPMC5825192 | biostudies-literature