HNMT C314T (rs11558538): Histamine Methylation

The HNMT C314T variant (rs11558538) is another polymorphism affecting Histamine N-Methyltransferase function. While less studied than the Thr105Ile variant, this SNP may also influence your body's ability to clear histamine from tissues, with potential implications for allergies, inflammation, and brain function.

HNMT Enzyme Review

Histamine N-Methyltransferase (HNMT) is essential for intracellular histamine degradation:

• Function: Methylates histamine to inactive N-methylhistamine
• Location: Inside cells throughout the body
• Key tissues: Brain, airways, skin, intestinal mucosa
• Importance: Only pathway for histamine clearance in the CNS

Understanding Your Genotype

• C/C: Reference genotype - normal enzyme function
• C/T: Heterozygous - may have slightly altered function
• T/T: Homozygous variant - potentially reduced activity

Research Context

The C314T variant has been studied in several contexts:

Inflammatory Conditions

• Some studies suggest association with inflammatory bowel disease
• May influence histamine's role in gut inflammation
• Potential link to inflammatory skin conditions

Allergic Disease

• Studied in context of asthma and allergic rhinitis
• May affect duration of allergic symptoms
• Could influence antihistamine effectiveness

Neurological Associations

• Histamine is a neurotransmitter affecting alertness, appetite, and cognition
• HNMT variants may influence baseline brain histamine
• Some research links to ADHD symptom severity

Combined HNMT Variant Effects

Having variants at both HNMT positions may compound effects:

Interaction with DAO/AOC1

The two histamine degradation pathways (DAO and HNMT) work in different compartments:

• DAO (AOC1): Handles histamine in the gut before it enters tissues
• HNMT: Clears histamine once it's inside cells

If both pathways are compromised:

• More dietary histamine enters circulation (DAO deficiency)
• Once in tissues, histamine persists longer (HNMT deficiency)
• This combination can lead to more severe and prolonged symptoms

Practical Implications

For Those with the T Allele

• Pay attention to overall histamine load
• Support methylation pathways (B vitamins, folate)
• Consider the relationship between allergies and diet
• Antihistamines may be particularly helpful

Methylation Support

Since HNMT requires SAM (S-adenosylmethionine) as a cofactor:

• Methylfolate: Supports SAM regeneration
• B12: Essential for methylation cycle
• B6: Supports SAM synthesis
• Magnesium: Required for many methylation enzymes

Natural Antihistamine Support

• Quercetin: Stabilizes mast cells, reduces histamine release
• Vitamin C: Supports histamine breakdown
• Stinging nettle: Traditional antihistamine herb
• Bromelain: May enhance quercetin absorption

Prevalence

• General frequency: The T allele is relatively uncommon
• Population variation: Frequency differs across ancestries
• Often analyzed alongside: rs1050891 for complete HNMT picture

When to Consider This Variant

The C314T variant may be relevant if you experience:

• Prolonged allergic symptoms despite treatment
• Histamine-type reactions that last longer than expected
• Symptoms affecting brain function (insomnia, anxiety, brain fog)
• Inflammatory conditions in skin or gut
• Known DAO/AOC1 variants with unexpectedly severe symptoms

Testing with NutraHacker

NutraHacker's Histamine Panel analyzes both HNMT variants along with all major AOC1/DAO variants, giving you a comprehensive picture of your histamine metabolism capacity.

Frequently Asked Questions

Is this variant as important as Thr105Ile?

The Thr105Ile variant (rs1050891) has been more extensively studied and has clearer clinical associations. However, C314T may contribute to overall HNMT efficiency. Analyzing both gives a more complete picture of your HNMT function.

Should I supplement with SAMe?

SAMe provides the methyl donor HNMT needs. However, SAMe supplementation can have side effects and may interact with medications. It's better to first ensure adequate B vitamins and methylation support, which naturally helps your body produce SAMe.

References

1. Preuss CV, et al. Human histamine N-methyltransferase pharmacogenetics: common genetic polymorphisms that alter activity. Mol Pharmacol. 1998;53(4):708-717.
2. García-Martín E, et al. Histamine pharmacogenomics. Pharmacogenomics. 2009;10(5):867-883.
3. Schwelberger HG. Histamine N-methyltransferase (HNMT) enzyme and gene. In: Histamine and Histamine Receptors in Health and Disease. Springer. 2017:53-89.