A forum to discuss Chronic Cerebrospinal Venous Insufficiency and its relationship to Multiple Sclerosis.
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Post by sbr487 » Wed May 02, 2012 5:54 am

Not totally relevant to CCSVI but certain portions are probably applicable.
Earlier efforts to hunt 
down disease-causing genes—so-called genomewide association studies—frequently came up empty-handed because medical researchers had to take cost-saving shortcuts. Instead of trolling an individual’s entire genome, they limited their search to dna regions where variations are most often seen across large populations. “It was assumed that common variants might be responsible for common diseases, but many diseases turn out to have many different rare variants at their root,” says James Lupski, a medical geneticist at Baylor College of Medicine in Houston. “That’s why the power of whole-genome sequencing blows us away. It’s the only way we can get at these rare variants.”
Quite a few gene study on MS, lot of them would conclude that they did not find anything specific to suggest that faulty genes.
Most of them look at genes that regulate immune system with the basic assumption that immune system is causing the problem.
Similar could be the case with MS also where we are looking at the wrong place for a clue ...
A new scientific truth does not triumph by convincing its opponents and making them see the light, but rather because its opponents eventually die and a new generation grows up that is familiar with it
- Max Planck

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Post by cheerleader » Wed May 02, 2012 7:14 am

It's really relevent, sbr. Dr. Ferlini has looked at the copy number variations in pwCCSVI and found a robust correlation with venous malformations and CNVs on the HLA locus associated with MS. There is much crossover in this area, because the genes that control venous development are related to the immune system. ... -final.pdf
Methods: In order to explore the presence of copy number variations (CNVs) within the HLA locus, a custom CGH array was designed to cover 7 Mb of the HLA locus region (6,899,999 bp; chr6:29,900,001-36,800,000). Genomic DNA of the 15 patients with CCSVI/VM and MS was hybridised in duplicate.
Results: In total, 322 CNVs, of which 225 were extragenic and 97 intragenic, were identified in 15 patients. 234 known polymorphic CNVs were detected, the majority of these being situated in non-coding or extragenic regions. The overall number of CNVs (both extra- and intragenic) showed a robust and significant correlation with the number of stenosing Vascular Malformations (Spearman: r = 0.6590, p = 0.0104; linear regression analysis r = 0.6577, p = 0.0106).
The region we analysed contains 211 known genes. By using pathway analysis focused on angiogenesis and venous development, MS, and immunity, we tentatively highlight several genes as possible susceptibility factor candidates involved in this peculiar phenotype.
Conclusions: The CNVs contained in the HLA locus region in patients with the novel phenotype of CCSVI/VM and MS were mapped in detail, demonstrating a significant correlation between the number of known CNVs found in the HLA region and the number of CCSVI-VMs identified in patients. Pathway analysis revealed common routes of interaction of several of the genes involved in angiogenesis and immunity contained within this region. Despite the small sample size in this pilot study, it does suggest that the number of multiple polymorphic CNVs in the HLA locus deserves further study, owing to their possible involvement in susceptibility to this novel MS/VM plus phenotype, and perhaps even other types of the disease.
Here is information on one specific gene, FAP48. FAP48 is found to contribute to venous malformations, and it is also found to modify t-cell immune response. Many genes, as Dr. Ferlini's study shows, have this kind of interaction, because the endothelium is involved in both the immune system and vasculature.

in venous malformations--
Venous malformation is a common type of vascular anomaly. Two genes have been identified for venous malformations, TIE2 for mucocutaneous venous malformations (MIM #600195) and glomulin for glomuvenous malformations (MIM #138000). . Boon et al.46 identified the first locus for GVM on chromosome 1p22-p21. The specific gene was later identified as the glomulin 47 (FAP48) gene coding for an FK506-binding protein (FKBP)-associated protein of 48 kD. ... ulares.pdf

in t cell activation--
In the present study, we provide evidence for an implication of FAP48 in the activation of T lymphocytes and for its antiproliferative properties. The involvement of target molecules in the signaling pathway of FAP48 is discussed.

to claim that the known genetic links of MS are purely about the immune system is wrong....even if we just look at the areas that have been studied in depth, we can see the crossover.
Husband dx RRMS 3/07
dx dual jugular vein stenosis (CCSVI) 4/09

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