DNA Methylation and HD

Posted: March 15, 2013 in Uncategorized
Tags: , , , , ,

For those that have not seen the first article I posted regarding methylation here it is: https://geneticpotential.wordpress.com/2013/03/12/dna-methylation-and-gene-expression/.

Interesting studies have come out within the last couple of months regarding methylation and Huntington’s Disease. One of which originated out of my home state of Massachusetts at MIT. The researchers found that cells with normal Huntington proteins had dramatically different patterns of methylation then the cells with the abnormal protein. Some gained methyl groups, while others lost them (http://www.medicalnewstoday.com/articles/255191.php).
If you remember from my previous article, methylation is a way for our body to turn off specific genes. If we can figure out how to normalize methylation, or at least imprve it we should be able to increase the age of onset for the disease. Ultimately this may even lead to a cure.
Another interesting fact from the study that I mentioned earlier was that the researchers determined that the abnormal protein specifically targets genes involved with brain function. The location also happens to be in the regions of the genome that controls the switching on and off of neighboring genes. Genes that are responsible for growth and function of the brain. If this is true then HD is not only a neurodegerative disorder, but it also blocks the brain’s ability to grow and function while destroying it. My question is still, why does this not happen earlier in life? How can someone live symptom free for 35-50 years?
This may be because methylation is not a fixed process. In fact it can change throughout the life cycle. Perhaps there is a normal methylation process early on in the disease and then something triggers a change which leads to a decrease in methyl groups and an increase in the expression of the abnormal Huntington protein.
In previous articles I also described how glutathione gets depleted and there is an increase in reactive oxygen species (ROS) within the cells. The depleted glutathione may set the stage for altered methylation. The methyl donor, methionine becomes depleted as glutathione becomes depleted (http://www.sciencedirect.com/science/article/pii/S0304383597003005). Less methionine equals less methylation. Oxidative damage takes time to leave its mark and just maybe one of those marks is decreasing methylation. Ths would allow for an increase in the expression of the abnormal Huntington gene.

Where I stand right now is if we can catch the disease early on with genetic testing we can monitor intracellular glutathione levels and make sure they stay at normal levels. At the same time we can use a highly nutritious diet and possably some supplementation to make sure that all the nutrients required for methylation stay up. It does not look like there is a problem with the methyltetrahydrofolate reductase (MTHFR) gene. A gene responsible for folate metabolism (http://www.jnrbm.com/content/4/1/12).

  1. Trish says:

    Methylation is affected by Epigenetics, which includes: diet, blood sugar regulation, exercise, lifestyle, exposure to chemicals, food sensitivities, emotions…..all these things can turn genes on or off… Look up “nutrients needed for liver detoxification pathways”. Methylation is one of the conjugation pathways in phase 2 liver detoxification. Here is a good diagram: http://tuberose.com/Graphics/liver-detox-pathway2.jpg


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