hemochromatosis (HH) and celiac disease [ 23 – 28 ], and in a recent case–control study of 29,096
Swedish individuals with biopsy-verified celiac disease, HH was associated..."
http://link.springer.com/article/10.1007/s10620-015-3791-9#page-1
Rick's SNP - Navigating the Genetics of Iron Overload |
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"Multiple reports have also described a link between the genetic iron overload syndrome hereditary
hemochromatosis (HH) and celiac disease [ 23 – 28 ], and in a recent case–control study of 29,096 Swedish individuals with biopsy-verified celiac disease, HH was associated..." http://link.springer.com/article/10.1007/s10620-015-3791-9#page-1
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I have been following articles by Dr. Muckenthaler ever since Two to Tango. She does publish on many topics, but it appears to me that she has a strong focus on unraveling the true mechanics of iron homeostasis. Therefore the HFE mutations are frequently featured in her papers. For example her latest paper is How mutant HFE causes hereditary hemochromatosis. In it she states: "...the underlying mechanisms differ: although the H63D variant failed to inhibit Alk3 ubiquitination, the HFE C282Y mutant protected ALK3 from ubiquitination, similar to wild-type HFE. The authors speculate that the HFE C282Y mutant protein that does not reach the cell membrane sequesters Alk3 inside cells, thereby preventing Alk3 from trafficking to the cell surface."
So our HFE mutations prevent increased Alk3 protein levels on the cell surface of hepatocytes (liver cells). Alk3 is critical to hepcidin expression. Without hepcidin, the body continuously recycles and absorbs iron leading to iron overload. This is a significant finding because hepcidin is a huge and complex molecule which is very difficult to whereas Alk3 may be easier to manipulate pharmacologically. For others that may be interested in keeping up with Dr. Muckenthaler, here is a handy link to her most recent publications. The previous article seemed promising but was not really. Two more to read in more detail and post out are http://onlinelibrary.wiley.com/doi/10.1002/1096-8652(200011)65:3%3C223::AID-AJH8%3E3.0.CO;2-9/pdf and http://asheducationbook.hematologylibrary.org/content/2003/1/40.full.pdf+html. One has detail on iron deficiency anemia caused by excessive phlebotomy and the other has a strong discussion on the penetrence issue.
I just printed this out to read over breakfast tomorrow morning. Hopefully it will have some insights that I will post on my site later. http://esciencecentral.org/journals/the-crosstalk-between-micro-rna-and-iron-homeostasis-2332-0672.1000112.pdf
I just read this and want to get it out to people fast since it is very important for anyone with cancer. The article is quite technical so I will try to summarize it including some additional background for the general person:
So, if you are currently fighting cancer it is very important to know your HFE variant status. Make sure your oncologist is up on this. Statins are given out too often in my opinion, but if it gives you a shot at survival then killing a few liver cells by taking it is not that big of a deal! Full text article I was referred to this link on FB and it has some current (2013) and complete listings on HFE. Seems even more detailed than malacards currently is. I want to do more research here and update my genetics page as needed. https://www.inkling.com/read/wintrobes-clinical-hematology-greer-13th/chapter-25/hfe-hemochromatosis-gene
So I found out about some different SNPs that are impacting my family's health and have gone down that rabbit hole for a while. This is the MTHFR that I have been commenting on, and this is way more complicated than HFE! For HFE folks the big issue is that the 'methylation' cycle mutations can affect your ability to create red blood cells and affect your ability to turn on and off protein production from your genes. So a bad C282Y gene could easily get stuck in the on state even if you are not eating a high iron diet. This would keep your TS score high and cause more cell damage than if the gene was shutting off normally. Easier 'cure' than HFE, just decypher your SNPs and learn what vitamins your body needs to skirt or support the methylation cycle and you are good to go. But that is a bit harder to figure out than it sounds. Methylated B12 is the best place to start for most people, but not all. It is a good test to buy a bottle and see if using it makes your mind less foggy. Lots more to come on this, but I wanted to say at least this much since I have gotten quiet on here. I do not think I have made an update on this site in 4 weeks. That is not meeting the standard that I want to hold myself to.
Gene mutations. Words make things seem different than what they are. Angelina Jolie's mutation made big news but does that make her a ... mutant? Consider this. Each of us have around 21,000 genes and EACH of us have rare mutations on around 150 of these genes. It is just the way of life with a genome. Mutations are not like turning into the Creature from the Black Lagoon. Sometimes they do bring a horrible illness or even just an annoying one. But some do things as odd as deciding whether or not we can smell asparagus in urine. Having a gene mutation is not inherently a bad thing that makes a person defective. It is simply a difference between us that makes our ancestors still a part of who we are today.
According to my wife's doctor many of his patients with HH also have a mutation on their MTHFR gene. This makes it so they cannot break down vitamin B12 (folate?) correctly. Because of this he says we should be taking a methalated form of B12 folic acid. I need to do some research on this and will report on it. I am hoping my 23andme test will cover the MTHFR gene! Those results should be in for us in about 3 weeks. He also suggested testing CD4 and CD8 cells for anyone with HH to see the overall effect the disease has had on us. He has some very interesting ideas on HH partially because he has a mutation as well, but it is not as impacting as HH. He further commented on thyroid involvement being very important to identify with HH and also that cortisol which is typically produced in 'fight or flight' scenarios and has a drastic impact on digestion. Apparently HH affecting thyroid can cause elevated cortisol which affects the ability to process our food and get the nutrients.
Turns out that 23andme tests for this but does not report it. One needs to use these links: https://www.23andme.com/you/explorer/snp/?snp_name=Rs1801133 https://www.23andme.com/you/explorer/snp/?snp_name=Rs1801131 The first link correlates to the C677T mutation with an A result in the DNA resulting in the T mutation in the protein. The second link correlates to the A1298C mutation with a G result in the DNA resulting in the C mutation in the protein. So if 23andme reports AA on the first link, then you are homozygous for the C677T mutation and should research what that means for you even though it is not described with the 23andme results! I wanted to get my thoughts down on the topic even though it needs some key answers. If it proves out then I will write it up in a web page. Here is the basic concept, C282Y causes a misfolded protein which no longer can exit the cell wall to get to its receptor in order to request the production of Hepcidin. Given that LDL cholesterol serves the purpose of cell repair and HDL cleans up the mess, does it follow that these misfolded proteins must be 'cleaned' up by cholesterol? If so, then a C282Y mutation would be autosomal dominant for elevated cholesterol AND that cholesterol would be necessary for cell health. Meaning that artificially lowered cholesterol from statin use could leave the body unable to keep up with repairs. Of course these proteins would only be produced while the body thinks it has too much iron - so keeping us in maintenance with a Ferritin under 50 may stop the creation of these misfolded proteins and reduce cell stress. Not so for those who go undiagnosed and continue to produce these misfolded proteins all of their lives. A statin seems like it could do even more harm in such cases. Late night thoughts on the night before a blood donation. Aren't I the life of the party. Further info - I had a chance to discuss this with my wife's doctor who also treats many HH patients. He agreed with my line of reasoning here but emphasized that the cholesterol increase should be thought of as a baseline increase and is not likely enough to be called 'high' on its own. Further he corrected me that LDL does not do repair, it is the delivery mechanism for the molecules that actually do the repair. And HDL goes to the site of the repair and provides transport for the remnants of the repair.
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AuthorMy name is Rick and the SNP which I refer to is a C282Y homozygous variant in my HFE gene. This site is devoted to making that sentence sound like simple English. Archives
July 2015
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