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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.

This gene, FAP48, is also noted as an immune modulating gene. 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.

Cece wrote:These are genes that are identified as playing a role in the immune system but they are also identified as playing a role in the vascular system? They overlap, in other words.

angiosenesis:Angiogenesis is the physiological process involving the growth of new blood vessels from pre-existing vessels.[1] Though there has been some debate over terminology, vasculogenesis is the term used for spontaneous blood-vessel formation, and intussusception is the term for new blood vessel formation by splitting off existing ones.[2]
Angiogenesis is a normal and vital process in growth and development, as well as in wound healing and in granulation tissue. However, it is also a fundamental step in the transition of tumors from a dormant state to a malignant one, leading to the use of angiogenesis inhibitors. The identification of an angiogenic diffusible factor derived from tumors was made initially by Greenblatt and Shubik in 1968.[3

Billmeik wrote:so the genes for angiogenesis and ms are similar. The group of genes the big study is about have a different name. (don't they? HTLA or something?)
The trick would be to find out if those ones apply to angiogenesis too.

cheerleader wrote:As soon as I can get the full Compston paper, I'll see if I can find any crossover betwen the newly illucidated MS genes, which may or may not be outside the HLA locus.

Dr. Alessandra Ferlini- geneticist at Universite deglie Studi di Ferrara
SNPs are single nucleotide polymorphisms- and they reveal a multi-loci susceptibility to MS. The 4 specific loci are MS1, MS3, MS4, MS2. These are the chromosomes most linked to MS

Genetics is still questioned in this research, since there are undefined environmental factors.

Genome inflation- a characteristic of SNPs may hamper the true definition of identified genetic loci by SNP association. More studies are needed.

Interactome- the interaction of phonemics, genomics, preteomic, metabolic studies- all together-
This is done in genomic studies using CGH array rather than SNPs

The Ferrara study looked at CNVs (copy number variations) of chromosome 6p21.32 (HLA locus) in CCSVI patients.
CGH verified the occurrence of CNVs in the major locus of MS patients.
15 unrelated CCSVI patients were tested. No relation between the topography of CNVs and phenotype were shown....
but there was a significant relation between the number of extragenic CNVs and the phenotype correlated with venous malformations.

HSPAIL, HSPIA, HSPIB (heat shock proteins) were related to angiogenesis and immunity. HLADLAZ and CD4 are involved in proinflammatory disease and tumor angiogensis. There are multiple gene disorders, and environment has a large influence.

The genome imbalance may be sensitive to environmental factors.

There was a significant correlation between the number of CNVs and the number of venous malformations. The number of polymorphic CNVs in the HLA region linked to MS does correlate with the number of venous malformations in MS patients.

This is a new way to study genetic disorders- to look for mutations on more than one genome. It is a very complex system, and cannot be narrowed to one genome.

Dr. Frohman asks if this has been tested in families? Are there genes affected in relatives with other autoimmune diseases?

Dr. Ferlini answers that this is a pilot study, and it is the first time looking at this paradigm. Future testing will look at families.

Dr. Lee comments that we have much genetic data on lymphatic malformation, yet no studies on the genetics of venous malformation. The veno-lymphatic systems need to be brought together. They have been separated and we need more venous information.

Dr. Ferlini comments that a similar phenotype can involve many genes, it depends on how they interact in the pathway. We need to locate many genes and understand how they interrelate, when they switch on and off, and how they interact in polygenetic disorders.

cheerleader wrote:This thread is suggested reading for those who are referencing Compston's study. Many of the "immunologic" genes associated with MS from the HLA locus have crossover into the vascular realm.

scorpion wrote:

cheerleader wrote:This thread is suggested reading for those who are referencing Compston's study. Many of the "immunologic" genes associated with MS from the HLA locus have crossover into the vascular realm.

I would suggest asking a genetic specialist about these so called connections instead of relying on anyone on a support forum, including me, to make any kind of scientific connections.