Re: Genes and environment in multiple sclerosis (layman's version)

[Guest guest]

I’ll take a shot at it. These are clearly NOT

written for the layman, but if you spend some time researching, you can pretty

much figure it out. I’ll provide links (Wikipedia) to some of the

terms. It’s not nuclear physics; I wish – would be a lot

simpler, for me!

points out that we’ve many times heard that

PSC is an autoimmune disease with genetic components, probably triggered by

some environmental insult. In other words, susceptibility to PSC results

from a combination of genes you inherited from your parents, along with some

sort of environmental trigger. Environmental triggers can be many things;

sunlight, malnutrition, chemicals, allergens, disease organisms, etc. As

Chaim stated, the prevalence of PSC in Scandinavians might lead one to think

that Vitamin D deficiency may be one trigger for PSC (ther are probably more

than one).

Now for the translation (bold italics). J

“Multiple sclerosis (MS) is a complex trait in

which allelic variation in the MHC class II region exerts the single strongest

effect on genetic risk.” We think we know the location of the

main genes associated with MS. MHC class II complex “Encodes

heterodimeric peptide-binding proteins and proteins that modulate antigen

loading onto MHC class II proteins in the lysosomal

compartment such as MHC II DM, MHC II DQ, MHC II DR,

and MHC II

DP” (http://en.wikipedia.org/wiki/Major_histocompatibility_complex).

I encourage you to look at the links – you’ll see things like digestive

enzymes, antigens (think immune system) and graft vs host disease (again,

immune system).

“Epidemiological (http://en.wikipedia.org/wiki/Epidemiology)

data in MS provide strong evidence that environmental factors act at a

population level to influence the unusual geographical distribution of this

disease. Growing evidence implicates sunlight or vitamin D as a key

environmental factor in aetiology.” Based on the

epidemiological studies of MS, it looks like vitamin D (deficiency) may be an

environmental trigger for MS.

“We hypothesised that this environmental candidate

might interact with inherited factors and sought responsive regulatory elements

in the MHC class II region. Sequence analysis localised a single MHC vitamin D

response element (VDRE) to the promoter region of HLA-DRB1. Sequencing of this

promoter in greater than 1,000 chromosomes from HLA-DRB1 homozygotes (http://en.wikipedia.org/wiki/Homozygotes)

showed absolute conservation of this putative VDRE on HLA-DRB1*15 haplotypes (http://en.wikipedia.org/wiki/Haplotypes).

In contrast, there was striking variation among non-MS-associated haplotypes.”

We thought that vitamin D might be the culprit, and confirmed a

relationship with DNA studies (genes again).

This abstract on MS, genes and environment concludes with

“These findings support a connection between the main epidemiological and

genetic features of this disease with major practical implications for studies

of disease mechanism and prevention.” That is, they’ve

shown a connection between the genetics and epidemiology of MS. If

you can show that connection, you’re on the track to treatment and

cure. This will NOT be easy or fast, but it constitutes a major breakthrough

(for MS).

See – nothin’ to it! J

Arne

UC

1977, PSC 2000

Alive

and well in Minnesota

…It is frustrating being so excited about some

great news or a possible break thru and not being able to understand it…