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Histamine N-methyltransferase (HNMT) is an enzmye which breaks down histamine and is encoded for by the HNMT gene 1.

Histamine plays an important role in the immune response, an in particular allergic responses. In health, histamine is released from immune cells (known as mast cells) resident in the skin, gut or lungs when a pathogen or allergen is detected. Histamine then generates three standard physiological responses 2:

  • Firstly, blood vessels are dilated to allow other immune cells to quickly reach the area where the pathogen was detected.
  • Secondly, smooth muscle contracts, which is thought to be a protective measure limiting other pathogens entering the body.
  • Finally, mucus secreting cells are stimulated, for example in the nose or gut, to protect against further pathogens reaching tissue. In health, histamine is then quickly degraded by HNMT and the immune system clears the pathogen.

As its name suggests HNMT functions by transferring a methyl group onto histamine, inhibiting its function; with HNMT using S-adenosyl-L-methionine (SAM) as a methyl donor. This inhibited histamine can then be excreted from the body 3.

There is one SNP in the HNMT gene which is associated with poor health outcomes, rs11558538 or C314T.


Science Grade
Immune Health
rsID Number Major Allele Minor Allele Minor Allele Frequency (%) Major Amino Acid Minor Amino Acid
rs11558538 c t 7 Thr Ile

Risk Description

The risk ‘C’ allele of C314T in the HNMT gene is potnetially associated with an increased incidence of developing Parkinson Disease. This SNP was described by two individual researchers and so initially was listed as both rs1801105 and rs11558538. However, the two records have been merged and rs11558538 is the official rsID.

There have been conflicting reports in the literature linking the risk ‘C’ allele of C314T with Parkinson Disease 4,5. However, a recent meta-analysis, or a study which compiles all previous studies together to increase sample size, has confirmed an association 6.

However, things get confusing at this point. Clinically Parkinson Disease is associated with an increased level of histamine 7, and so it would be expected that the risk ‘C’ allele of C314T would lead to a reduction in HNMT enzyme activity, thus leading to histamine accumulation. Interestingly it is actually the ‘T’ allele, which is associated with a reduced risk of developing Parkinson Disease that displays reduced enzyme activity 8. There is currently no known mechanism linking these two apparently conflicting pieces of information, and so further research is required to definitively determine risk, and also a mechanism.

There were some suggestions that C314T may be linked with an increased incidence of childhood asthma or restless leg syndrome, however these have now both been disproved.

Discuss this information with your doctor before taking any course of action.


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