Critical Review: Disseminated Sclerosis

Brain, W. Russell

doi:10.1093/qjmed/os-23.91.343

Cited by 81 publications

(22 citation statements)

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“…The female-to-male ratio was near unity in North America at the turn of the 20th century, 17 and today, a ratio of 2:1 is common despite regional variations. In Canada this ratio has been increasing for at least 60 years, and now surpasses 3.2:1, 6 while in Scotland a change in sex ratio from unity to more than 3:1 has taken place since the 1950s.…”

Section: Hla-drb1mentioning

confidence: 94%

MHC transmission

Chao¹,

Ramagopalan²,

Herrera³

et al. 2011

Neurology

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Objective: Major histocompatibility complex (MHC) genes dominate genetic susceptibility factors in multiple sclerosis (MS). Given the general consensus that incidence and prevalence of MS has been rising and specifically in women, we evaluated MHC-gender interactions. Methods:In a large family-based cohort consisting of 7,093 individuals (2,127 affected individuals) from 1,055 MS families, we examined MHC transmission by family structure and gender stratified by genetic distance of affected relatives from the MS proband. Conclusions: These observations implicate the MHC as the site of interactions and modifications mediating the female-to-male gender ratio in MS and its progressive increase. They further suggest this occurs via gene-environment interactions and epigenetic modifications in this region. ResultsThe difference between collateral and nuclear families provides some insight into the inheritance, decay, and gender specificity of putative epigenetic marks. Neurology The etiology of multiple sclerosis (MS) remains unclear; however, several lines of evidence suggest that MS is an acquired autoimmune disease and is triggered by environmental factors in genetically susceptible individuals. 1The main genetic contribution in MS comes from the major histocompatibility complex (MHC), and more specifically the human leukocyte antigen (HLA) Class II genes.2,3 Additional epistatic interactions and suppressor effects have also been observed within this locus. 4,5 There is general consensus that the incidence and prevalence of MS has been rising with an increased penetrance among women, 6 and excess monozygotic (MZ) twins concordance for MS is almost entirely female specific.7 Moreover, there is a maternal parent-of-origin effect 8 with higher number of affected mother-daughter pairs and few father-son pairs. 9There is little known about how the MHC might interact with the observed gender bias in MS. Since HLA alleles carry the strongest genetic susceptibility factors, we reasoned that the reported gender predisposition could be MHC-mediated. 10 Here we have used a large familye-Pub ahead of print on January 5, 2011, at www.neurology.org.

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Section: Hla-drb1mentioning

confidence: 94%

MHC transmission

Chao¹,

Ramagopalan²,

Herrera³

et al. 2011

Neurology

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“…misdiagnosis of hysteria in women with MS; over diagnosis in men because of their dominance in the workforce) rather than fact. From 1870 to 1910, there were only anecdotal reports, with suggested sex ratios ranging from virtual unity to prominence in one sex or the other [1,2]. A case series review of almost 2000 patients' records from the early 1900s showed that men were more affected than women with a male:female distribution of 3:2 [3].…”

Section: Introductionmentioning

confidence: 99%

European Charcot Foundation Lecture: The natural history of multiple sclerosis and gender

Sadovnick

2009

Journal of the Neurological Sciences

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“…For quite some time, MS was regarded as a disease of men, possibly due to substantial under-diagnosis of this condition among women [5,6] . However, this elusive notion gradually started waning, when an increase in sex ratio (female:male) from 1.9 to 3.2 was observed in birth cohorts of MS patients born during 1936-1940 and 1976-1980 in Canada [3] .…”

Section: Introductionmentioning

confidence: 99%

Retrospective Cohort Study of Gender Differential in Risk of Multiple Sclerosis in Kuwait

et al. 2016

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Background: Despite an increase in the incidence of multiple sclerosis (MS) in the Middle-East, there is a paucity of published data on sex ratio among MS patients in the region. Therefore, this retrospective cohort study determined sex ratio by year of birth of MS patients born from January 1, 1950, to December 31, 2000, who were diagnosed and registered in the Kuwait National MS Registry till April 30, 2013. Methods: Patients were classified into 5-year periods according to their year of birth. Sex ratio (female:male) and its 95% CI for each period were computed. Using binomial logistic regression, sex ratio in MS patients was modeled with respect to year of birth and nationality. Results: Of 1,035 patients with MS, 675 (65.2%) were women and 798 (77.1%) Kuwaiti. Sex ratio (female:male) of MS cases for entire study period was 1.9 (range 0.4-3.0). Multivariable logistic regression model showed that with each passing year of birth, there was statistically significant 8% increase in sex ratio (female:male) for vulnerability to MS risk (adjusted OR 1.08; 95% CI 1.06-1.09; p < 0.001). Conclusions: There was a statistically significant steady increase on logarithmic scale in the gender disparity for MS risk over the study period. This study from the Middle-East adds to the existing persuasive evidence of enhanced MS risk in women. Further insight in the context of differential risk factors including the role of sex hormones and vitamin D deficiency in MS pathogenesis may help designing preventive strategies.

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Critical Review: Disseminated Sclerosis

Cited by 81 publications

References 0 publications

MHC transmission

MHC transmission

European Charcot Foundation Lecture: The natural history of multiple sclerosis and gender

Retrospective Cohort Study of Gender Differential in Risk of Multiple Sclerosis in Kuwait

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