ME and My Genes

I've been putting off writing this post for a myriad of reasons but mostly because it is seriously complicated and I haven't sorted all of it out yet.  Also I'm in the middle of my winter crash so no energy to think about it much and not enough brain power to write about it coherently.  As a result this might turn out a bit rambly.

At the end of last year, I sent my spit off to 23andMe to have a very small subset of my genes decoded.  I got the results back in January.  However, before I get to the interesting bits I'm going to write about genetics in general because, in this case, context is VERY VERY important.

Right now decoding our genes is in its infancy so interpretation is still quite shaky and often wrong.  While it sent me into geek heaven to have it done, I also have a fairly good understanding that the results are probabilistic and NOT deterministic.  What does that mean?  Genes are a set of instructions on how to build a cell.  Each time a cell is built it only uses a subset of those instructions.  We have yet to fully understand why some instructions are used and others ignored.  This is the new field of epigenetics and the basic idea is that specific genes are expressed (turned on and off) after environmental exposures such as food, toxins, exercise, etc.  So even when they say that you have a mutation at such and such a location, while you do indeed have the mutation, you may or may not get the illness/trait associated with it.  So in reality it is a bit of a crap shoot whether these predictions will come true or not.  The short version is that our genes/cells are influenced strongly by our environment, such as food, toxins, exercise, etc.  Whether a particular gene actually gets expressed (flipped on/replicated), can only be predicted as a percentage not an actuality. That said, some mutations are more readily predicted than others so genetics tests are ranked by probability.  For a more in depth view I suggest watching PBS' Cracking Your Genetic Code which is available on their website and on Netflix.

So, be warned, if you decide to go this route: 1) once the answers are seen they can not be unseen (i.e. do you really want to know the probability of getting breast cancer or Alzheimer's?) and 2) it is only a prediction and not a concrete reality.

On the flip side if the genetic markers are there and you are having symptoms that line up with those markers you might be able to adjust your treatments so that you end up improving.

Okay, now the juicy details....

Since the FDA has gone after 23andMe, they have stopped producing the medical reports but they will still supply you with the raw genetic data.  This is what I got.  I downloaded my raw data and then paid Promethease $5 to translate it for me.  The interface is extremely wonky and you have to watch the tutorial vids to make any sense of it at all.  There are more expensive interpretation services out there but I haven't tried them yet.  I'm guessing that the interfaces are a tad better.  Anyway....

The answers come ranked by probability.  The most likely being first which is normally your gender (this gets into an entirely different long discussion about intersex, transgender, etc).  Promethease ranks them by an arbitrary probability number.  I'm not entirely sure what they use to generate this number but basically I chose to only pay attention to those of rank of 3 or higher.  My gender was rank 3.9.

Their database is incredibly detailed and interlinked so you can sort by disease, rank, probability, number of papers published regarding that particular mutation,  and many others.  I decided to look at rank 3 or higher but also with three or more published papers associated with that mutation.  Several interesting things popped out:

1. I have two mutations in MTHFR
2. Due to one or more mutations I have an inactive CYP2C9 gene
3. I'm of northern European decent.  

Now the MTHFR is what is causing the methylation cycle problems.  Since I have both the symptoms and a high probability of MTHFR issues it stands to reason that this one is true and active in my system.  I still have lots to read about MTHFR since there are entire websites devoted to the defect and what to do about it.  More than likely this will be the bulk of my research for the coming year.  Right now I am using methyl B12 and methyl folate and staying away from folic acid.  These supplements will replace what my body can not produce due to the mutations.

Another issue with MTHFR, is that I have to get my homocysteine levels checked regularly.  Right now mine are normal.  

The CYP2C9 causes a liver problem.  This is another one I have to research more fully but as of right now I know that a lot of the newer drugs assume that you have a working CYP2C9 so that they can be metabolized.  Since mine is shut off I can't metabolize these drugs and they build up in my system and cause side effects.  In particular I can't take Warfarin, Plavix, Tamoxifen and most of the NSAIDs.  Basically I need to assemble a list of drugs I shouldn't take.

I'm not completely sure but it also might cause problems with general detoxification but I have to look in to that for verification.  (It is one of those muddy memories that I can't find the citation for to back it up.)

Of course I had a handful of other results but they had a lower risk to them and I haven't done enough research to figure out if they are significant or not.  Just for your curiosity, I'm at increased risk for type 2 diabetes, melanoma, celiac, breast cancer and coronary artery disease.  These are the ones I'm not worrying about since I don't think there is enough statistical evidence to back up the probability that I'll actually contract these illnesses.  The other two, MTHFR and CYP2C9, I believe are in full swing and require my immediate attention.

Interestingly, my CFS treating doc backed me up on this and has referred me to a geneticist.  I haven't made an appointment yet.  I've been sick on sick on sick lately and need to wait until I feel better to make the trip into Boston to see the guy.

I was hoping for a more thorough ancestry but I have a 40-60% chance of being of northern European decent which is the area of Germany, Poland, Norway, etc.  I find this very interesting.  I know  that I'm English for at least five generations.  Maybe I'm from Viking stock.  Curiouser and curiouser....