A gender explanation? "Endogenous retroviral genes, Herpesviruses and gender in MS"

WillowJ

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Perron H, Bernard C, Bertrand JB, Lang AB, Popa I, Sanhadji K, Portoukalian J. "Endogenous retroviral genes, Herpesviruses and gender in Multiple Sclerosis." J Neurol Sci. 2009 Nov 15;286(1-2):65-72. Epub 2009 May 17. Review. PMID: 19447411

Abstract

Unexpected findings on endogenous retroviral elements expressed in cells from patients with Multiple Sclerosis appear to open a new avenue of research, after years of research dedicated to the understanding of their biological significance in human health and disease. Human endogenous retroviral family W (HERV-W) RNA present in circulating viral particles (Multiple Sclerosis associated RetroViral element, MSRV) has been associated with the evolution and prognosis of Multiple Sclerosis.

HERV-W elements encode a powerful immunopathogenic envelope protein (ENV) that activates a pro-inflammatory and autoimmune cascade through interaction with Toll-Like Receptor 4 (TLR4) on antigen-presenting cells, and triggers superantigen-like dysregulation of T-lymphocytes. HERV-W/ENV antigen has further been shown to be an upstream inducer of immunopathogenicity like that in MS and has repeatedly been detected in association with MS lesions in post-mortem brain studies. ENV protein now represents a novel target in MS, in our ongoing development of a neutralising therapeutic antibody.

We here review the pieces of a puzzle, which now offer a consistent picture for Multiple Sclerosis aetiopathogenesis. Interestingly, at the gene-environment interface, this picture also includes gender-related specificities through the potential interplay with endogenous retrovirus type W copies present on the X chromosome.
 

WillowJ

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higher genetic susceptibility to a diseases more women get, via x-linked genes (on "junk" DNA/ endogenous retroviruses). Maybe that could be applicable to other diseases as well, which also have more women patients.

This would lead to a scenario where more women would have such a disease, some women could potentially have the disease more severely (if multiple alleles influenced severity), men could still have the disease, men would inherit a genetic predisposition from their mothers (but not from their fathers), women could inherit a genetic predisposition from either parent.
 

Merry

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Thank you, Willow. What an amazing little universe the immune system is - and this play of genetics. I wish I could comprehend the whole shebang.
 

Mark

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Here's another gender explanation published recently (Ebers, Neurology)...I've also posted this on this related thread:
http://forums.aboutmecfs.org/showthread.php?9453

It's a couple of weeks old, sorry I'm only just getting round to posting. Would seem well worth looking into the details of this genetic link that's been found, and how that relates to the ERV study. I personally think that saying this is 'the explanation' of why women are (nowadays) more likely to suffer MS (they didn't used to be) is a typically overstated headline, but it's a very significant clue...

I kind of like the point made at the end of the Nursing in Practice article:
"scientists played down suggestions that the rise in MS among females was caused by genetic factors alone because the increase had occurred in such a small space of time."

I think the obvious way to think about this is to say that there's some 'new environmental factor' that disproportionately affects women - for the genetic reasons identified in these studies - and that environmental factor has been steadily rising in a short space of time. The "short space of time" we're talking about is the time period when autism, MS, ME, allergies and more have been increasing in prevalence...

The "environmental factor" just might, just conceivably might, be some kind of virus, of course...;)

http://www.nursinginpractice.com/article/23971/Women_%22more_likely_to_have_MS_gene%22

http://www.heraldscotland.com/news/...-multiple-sclerosis-hits-more-women-1.1078836

http://news.scotsman.com/news/Revealed-why-women-more-likely.6684762.jp

Revealed: why women more likely to suffer MS
Published Date: 10 January 2011
By Lyndsay Moss
RESEARCHERS have discovered why multiple sclerosis is more common in women than men.
They found women with MS are more likely to have a gene associated with the condition than men. Women are also more likely to pass this gene on to their daughters, according to the MS Society-funded study at the University of Oxford.

MS is the most common neurological condition affecting young adults in the UK, causing serious problems with movement and balance. Scotland has one of the highest rates of MS in the world, although the reasons for this remain unclear.

The new research, led by Professor George Ebers and published in the journal Neurology, analysed the genes of more than 7,000 people from some 1,000 families affected by MS to try to establish why some people seem to inherit MS, while others do not. The study found women appeared more likely to inherit genes linked with MS from a female relative.

In the 1950s, the numbers of men and women living with MS in Scotland were roughly equal. But today, the condition may affect as many as three times more women than men.

The research also offers an explanation as to why, in high prevalence areas, some 20 per cent of MS cases have at least one affected relative.

The scientists said the link to genes was only half the story, as these increases had taken place over too short a timescale to be explained as simply genetic.

Instead, the study suggests, the rise of MS in women is triggered by an interaction between genes and environment that specifically affects women.

Dr Jayne Spink, director of policy and research at the MS Society, said: "The exact cause of MS is still unknown, but this study helps solve a vital part of the puzzle."
 
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