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another post about B6 mentions the Dao mutation
http://www.geneticlifehacks.com/histamine-intolerance-genetics-part-2/
Please read through part 1 for more background on Histamine Intolerance. For a good overview of histamine intolerance, visit the Histamine Pirate site: Histamine Intolerance.
Causes of Histamine Intolerance
There are three main causes of histamine intolerance: too little DAO enzyme to breakdown histamines, too much histamine from gut microbes, or problems with histamine receptors.
Histamines are broken down and excreted through the diamine oxidase enzyme (DAO) and the histamine methyltransferase (HMNT) enzyme.
The DAO (diamine oxidase) enzyme metabolizes histamine into imidazole acetic acid. Genetic polymorphisms of the ABP1 gene can affect how much DAO enzyme is produced. Some of the polymorphisms that are included with 23andMe results are listed below. There are several other polymorphisms related to DAO production that are not included with 23andMe v.4 testing. [ref] [ref]
Check your 23andMe results for rs10156191:
- CC: normal
- CT: reduced production of DAO
- TT: reduced production of DAO
Check your 23andMe results for rs1049742:
- CC: normal
- CT: reduced production of DAO
- TT: reduced production of DAO
Check your 23andMe results for rs1049793:
- CC: normal
- CG: reduced production of DAO
- GG: reduced production of DAO [ref]
HNMT (histamine n-methyltransferase) is a gene that regulates histamine through metabolizing it from histamine to N-methylhisamine. Again, there are other mutations with the HNMT gene that are not included with 23andMe.
Check your 23andMe results for rs1050891:
- AG: reduced breakdown of histamine compared to GG
- AA: reduced breakdown of histamine compared to GG [ref]
According to a 2006 study, those with CT for rs11558538 have reduced HNMT activity. This SNP is identified on 23andMe as i300469. The wildtype is C.
Check your 23andMe results for i300469:
- CT: reduced breakdown of histamine compared to CC
- CC: normal [ref]
Methylation Cycle:
The methylation cycle plays a role in breaking down monoamine neurotransmitters including histamine. So looking at your methylation cycle issues can also help with balancing out a histamine intolerance. For anyone taking nicotinamide (also called niacinamide), here is an interesting research paper looking at the increase in plasma histamine level after taking 100 mg of nicotinamide.
Histamine Receptors:
The other side of the histamine equation is the histamine receptors to which histamine binds.
H1: smooth muscle, endothelium (cells lining the inside of blood vessels and lymph vessels), central nervous system tissue, mast cells (discovered in 1966)
H2 -Gastrointestinal, vascular smooth muscle tissue (walls of blood vessels), mast cells H2 receptors are blocked by Tagamet. (discovered in 1972) “H2 receptors mediate histamine stimulation of gastric acid secretion and may be involved in cardiac stimulation”
H3 – Central nervous system and some peripheral nervous system, mast cells (discovered in 1987) “feedback inhibitors in CNS”
H4 -bone marrow, basophils (type of white blood cell), thymus, small intestine, spleen, colon, mast cells (discovered in 2001) “considered to have a role in a number of inflammatory disorders such as allergy, asthma, chronic puritus and autoimmune diseases” [ref]
In the intestines, which is the body’s largest immune organ, mainly three types of histamine receptors have been found: H1, H2, and H4. Low levels of H3 were found in intestinal samples in a few of the study participants. Interestingly, those with food allergies and IBS had significantly higher levels of H1 and H2 receptors in their intestines. [ref]
There are genetic variations that contribute to the distribution of histamine receptors. Could that play a role in histamine intolerance?
Mast Cells:
Mast cells are the storage site for histamine in most tissue. Allergens cause mast cells to burst (degranulate) and release histamine. Large numbers of mast cells are in the skin, bronchial tree mucosa, and intestinal mucosa. Some think that histamine intolerance is a subset of MCAS (mast cell activation syndrome).
http://www.geneticlifehacks.com/histamine-intolerance-genetics-part-2/