Thursday, 19 January 2012

Genetics questions

We had a couple of interesting genetics related questions from Tim that we decided it was worth making a full post about.

The first was "So genes do change to take account of environmental factors then where does that leave the inuit peoples who have low incidence of MS and a shortage of sunlight?"

The environment can influence the genome in at least three ways which differ in timescales:

Genes change over time (generations) as a result of natural selection (genetic variants that give us an advantage to live in certain conditions become more common over time). An elegant recent study comparing the genomes of 61 different populations across the world has shown how our genomes have adapted to the different climates over the world.

Within our own lifetime, the environment influences our epigenome (chemical changes to the DNA sequence). A recent notable example is how smoking influences DNA methylation (adding of methyl groups) of the F2RL3 gene.

We will spend more time talking about epigenetics in the near future.

More immediately (within minutes/hours), genes respond to the environment through gene-environment interactions. For example we have shown that circulating vitamin D controls the levels of genes involved in MS.

Inuit populations such as those in Canada live at high latitudes (and thus low sunlight exposure) but have a low rate of MS. In fact the only cases of MS identified in this group are from people who have a mixed race background (Caucasian and Inuit parents). This may argue that vitamin D may not be important for MS. However, Inuits have a very,very high frequency of a gene that is strongly protective for MS- this is the concept of a gene-environment interaction- you need the 'wrong' genes being exposed to the 'wrong' environment. Having just the genes or just low vitamin D is not enough- you need both.


If vitamin D is a factor the Swedish migrant study would have had different results, would it not?

No, again this is the same gene-environment concept as before. Iranians for example have a similar genetic background to Caucasians (they carry a high frequency of MS risk genes), but in Iran they are not as likely to be exposed to sunshine/vitamin D deficiency as they are in Sweden. In Sweden they have the wrong environment, which acts on their genes and increases their risk of MS.

17 comments:

  1. The linked abstract is about Inuit-Caucasian people but it doesn't say that only mixed-race Inuits get MS.

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  2. This has been studied intensively in Canada- no individual with purely First Nations/Inuit heritage has been found to have MS- e.g.
    http://www.ncbi.nlm.nih.gov/pubmed/8719043

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  3. On our street, two of us, weirdly, both have MS. There's me (white, British) and an Asian kid a few doors down (British, Pakistani). I wonder if he has a similar genetic background to Caucasians?

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  4. Please say something about this-
    www.msra.org.au/progress-environmental-effects-ms-especially-vitamin-d

    It says that sun exposure is linked to MS risk independent of Vit D levels

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  5. More detail here www.cresunandhealth.org.au/story/msd.jsp

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  6. "I wonder if he has a similar genetic background to Caucasians?"

    I think so- studies in Indian MS patients show they have the same genes that increase MS risk as those as Caucasian MS patients.

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  7. "It says that sun exposure is linked to MS risk independent of Vit D levels"

    This study by the Ausimmune team is interesting in that it shows that measures of MS'ers sunshine exposure seems to be associated independently of vitamin D levels taken at the time of MS onset (people who developed MS reported lower sunshine exposure before they got MS and their blood level at MS onset had lower levels of vitamin D than controls).

    BUT, the issue is that the researchers did (could) not measure vitamin D levels at the same time as sunshine exposure- so they can't actually make a definitive conclusion that sun exposure acts independently of vitamin D.

    As Alberto Ascherio and colleagues wrote about the paper:
    "Although a direct protective effect of UV is possible, it is not necessary to explain the results of Lucas et al., which are consistent with the simpler hypothesis of a protective effect of vitamin D"

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  8. It seems there is a slim chance that this UV ray theory is right. Maybe we should try to get some sun when possible in addition to taking vit d, just in case

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  9. Re: Australian Vitamin D study. I note that you state that Albert Ascherio purported to make comments about 'the paper'. As far as I am aware the results of this section of the Ausimmune study are not due to be published in the journal Neurology until July. Where and what are you referring to please in regards to comments claimed to have been made by Ascherio?

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  10. Lucas study-

    http://www.ncbi.nlm.nih.gov/pubmed/21300969

    Ascherio response-

    http://www.ncbi.nlm.nih.gov/pubmed/21968847

    Both paywalled.

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  11. Moved to Check Q & A together
    Brightangel said...

    My apologies, Lucas will publish in Neurology in July in relation to EBV.
    Sunday, January 22, 2012 12:41:00 PM

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  12. Sunshine MS and Vitamin D

    If part of the vitamin D effect is in utero (in the womb), as could be suggested by the month of birth effect. Then the issue of vitamin D levels in MSers at onset etc may be irrelevant. This adds an extra level of complexity

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  13. Did you know that MS is more frequent in the northerly hemisphere especially northern European countries! Ticks are also more common in Northern European countries and they thought/think that MS was triggered by lack of sun/vitamin D. Good theory but Inuits for example are not known to have many MS cases, then they have a lot of snow etc……….so not good tick habit.

    So then is MS caused by Borreliosis (aka Lyme disease) and other tick related infections? The testing for Lyme disease is extremely poor for a latent infection and the test manufacturers state at best 41% accurate.

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    Replies
    1. Yes we were well aware that MS is higher in Northern Europe than Southern Europe. It's also more common in more Southern latitudes in the Southern hemisphere. Not sure what the tick/Borrlia situation is in the Southern hemisphere.

      Inuits have a genetic background that makes them less susceptible to MS.

      The Lyme disease hypothesis would seem to be not proven.
      http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1033030/

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    2. The inuit diet includes fish, seal, whale, caribou, birds and eggs, inseason berries, roots and seaweed. Foods that have vit D.

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  14. HI MouseDoctor2,

    Maybe you would like to read and "watch" http://www.unionsafety.eu/docs/HSNewsItems%2012/LymeDiseaseInvisibleAndMisdiagnosedDevastatesSufferersAsNHSAndGovRemainIdle%20.html

    Please note that Lyme disease is extremely difficult to diagnosis and the pubmed article relies on borrelia antibodies. People with latent Lyme disease can have negative results as clearly mentioned in the Invetech Lyme disease test instructions http://www.invitech.co.uk/downloads/instructions/CF-E601-801_C6_for_Europe_PI.pdf
    + the test is only 41% sensitive at detecting latent Lyme disease as you can see in the instructions. The HPA use this test but state it to be 99% sensitive (what could they be hiding)? So where are these missing undiagnosed misdiagnosed patients? THE CDC in America have concluded that true numbers of Lyme disease from 30,000 to 300,000 per YEAR SOURCE http://www.cdc.gov/media/releases/2013/p0819-lyme-disease.html So in the UK that would mean there is approx. 14,000 cases not reported or undiagnosed/misdiagnosed!

    "Diagnosis of late-stage Lyme disease is often complicated by a multifaceted appearance and nonspecific symptoms, prompting one reviewer to call Lyme the new "great imitator."[85] Lyme disease may be misdiagnosed as multiple sclerosis, rheumatoid arthritis, fibromyalgia, chronic fatigue syndrome, lupus, Crohn's disease, HIV or other autoimmune and neurodegenerative diseases." SOURCE;- http://en.wikipedia.org/wiki/Lyme_disease

    SO how many of these patients are being misdiagnosed with MS?

    Oh by the way I am not saying every MS patient has Lyme disease, but I believe there is a significant number.

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    Replies
    1. Nervous system lyme disease: is there a controversy?
      Halperin JJ.

      Infection with the tick-borne spirochete affects the nervous system in well-defined ways. Accurate diagnostic tools and effective therapeutic regimens are now well established.Virtually every known neurologic disorder has been blamed on this Lyme Disease and for most evidence is scant, nonexistent, or coincidental.

      I'll let ProfG deal with this one if he has time.

      Delete

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