Thursday 16 January 2014

Endogeneous viral genes are associated with MS susceptibility

The black swan is circling; when will it land? #MSBlog #MSResearch

"The study below links genetic markers close to where a member of the human endogenous retroviruses resides in our genomes with MS susceptibility and MS severity. Rule one with these types of studies is to ask others to reproduce the result. This could easily be done using data from the International MS Genetics Consortium. The odds are it won't be reproduced; only 5% of studies like this get reproduced."

"If the results are reproduced  this would be very interesting indeed and would pose a long list of questions about whether or not these genetic variants have biological effects and how we can link these effects to MS biology. The authors discuss some speculative ideas around this theme in their discussion."

"As you can see this virus resides on the X, or female chromosome, hence females have two copies. Whether or not this has any relevance to the female preponderance of MS is also of interest."

"The good news about this paper is that another reasearch group is exploring the link, or putative link, between MS and viruses, in this case a specific HERV. Let's hope their hypotheses lead us closer to the cause of MS. It always takes out-of-the-box thinking to change the paradigm. We need to keep an open mind about alternative explanations about the pathogenesis of MS; particularly since the autoimmune dogma has many holes and inconsistencies in it."


"Is their a black swan circling? For those of you interested in the black swan analogy should read my previous post on this topic: click here."

Epub: GarcĂ­a-Montojo et al. HERV-W polymorphism in chromosome X is associated with multiple sclerosis risk and with differential expression of MSRV. Retrovirology. 2014;11(1):2.

BACKGROUND: MS is an autoimmune demyelinating disease that occurs more frequently in women than in men. MS Associated Retrovirus (MSRV) is a member of HERV-W, a multicopy human endogenous retroviral family repeatedly implicated in MS pathogenesis. MSRV envelope protein is elevated in the serum of MSers and induces inflammation and demyelination but, in spite of this pathogenic potential, its exact genomic origin and mechanism of generation are unknown. A possible link between the HERV-W copy on chromosome Xq22.3, that contains an almost complete open reading frame, and the gender differential prevalence in MS has been suggested.

RESULTS: MSRV transcription levels were higher in MSers than in controls (U-Mann-Whitney; p = 0.004). Also, they were associated with the clinical forms (Spearman; p = 0.0003) and with the Multiple Sclerosis Severity Score (MSSS) (Spearman; p = 0.016). By mapping a 3 kb region in Xq22.3, including the HERV-W locus, we identified three polymorphisms: rs6622139 (T/C), rs6622140 (G/A) and rs1290413 (G/A). After genotyping 3127 individuals (1669 MSers and 1458 controls) from two different Spanish cohorts, we found that in women rs6622139 T/C was associated with MS susceptibility: [chi2; p = 0.004; OR (95% CI) = 0.50 (0.31-0.81)] and severity, since CC women presented lower MSSS scores than CT (U-Mann-Whitney; p = 0.039) or TT patients (U-Mann-Whitney; p = 0.031). Concordantly with the susceptibility conferred in women, rs6622139*T was associated with higher MSRV expression (U-Mann-Whitney; p = 0.003).

CONCLUSIONS: Our present work supports the hypothesis of a direct involvement of HERV-W/MSRV in MS pathogenesis, identifying a genetic marker on chromosome X that could be one of the causes underlying the gender differences in MS.