rs10156191 — AOC1 (DAO) Thr16Met
DAO structural variant affecting enzyme activity and histamine degradation
Details
- Gene
- AOC1 (DAO)
- Chromosome
- 7
- Risk allele
- T
- Protein change
- p.Thr16Met
- Consequence
- Missense
- Inheritance
- Codominant
- Clinical
- Risk Factor
- Evidence
- Strong
- Chip coverage
- v3 v4 v5
Population Frequency
Ancestry Frequencies
Category
Methylation & DetoxDAO Structural Variant - When the Enzyme Itself Is Altered
While rs2052129 affects how much DAO enzyme your body makes, the Thr16Met 11 Threonine to methionine at position 16 variant (rs10156191) changes the actual structure of the enzyme protein. This is a missense mutation 22 A missense mutation changes one amino acid to another in the resulting protein that substitutes threonine with methionine at position 16, potentially altering the enzyme's ability to bind and degrade histamine.
The Mechanism
The amino acid change at position 16 occurs in a region of the protein that
influences its folding and copper-binding ability. DAO is a copper-dependent enzyme 33 DAO requires copper ions at its active site to catalyze the oxidation of histamine,
and structural changes near the active site can reduce catalytic efficiency. The
T allele produces an enzyme that is less effective at breaking down histamine, even
when produced in normal quantities. Ayuso et al.44 Ayuso et al.
Ayuso P et al. Genetic variability of human diamine oxidase. Pharmacogenet Genomics, 2007
found that carriers of the variant allele had reduced serum DAO activity compared
to non-carriers.
Clinical Significance
This variant is frequently studied alongside other AOC1 variants to determine
overall DAO haplotype status. Research by Maintz et al.55 Maintz et al.
Maintz L & Novak N. Histamine and Histamine Intolerance. Am J Clin Nutr, 2007 and others has shown that
carrying multiple DAO risk variants (across rs2052129, rs10156191, and rs1049793)
has an additive effect on reducing enzyme activity. An individual who is heterozygous 66 Heterozygous means carrying one normal and one variant copy of a gene
at all three positions may have more impaired DAO function than someone who is
homozygous at just one. The variant is notably more common in African populations
(T allele ~51%) compared to East Asian populations (~11%).
What This Means for You
If you carry the T allele here, evaluate your overall DAO status by considering all three AOC1 variants together. Mild impairment at one position can often be compensated, but compound impairment across multiple variants may tip the balance toward clinically meaningful histamine intolerance. Practical dietary strategies remain the same: fresh foods, low-histamine choices, and DAO supplements with meals if needed.
Nutrient Interactions
Genotype Interpretations
What each possible genotype means for this variant:
Normal DAO structure
Normal DAO enzyme structure at this position. About 55% of Europeans share this genotype.
One structural DAO variant
You carry one structural variant that may reduce DAO activity. Combined with other DAO variants, this affects overall histamine clearance in the gut. About 37% of Europeans share this genotype.
Reduced DAO structure/function
Two structural variants reducing DAO function. About 8% of Europeans have this genotype. Consider low-histamine dietary approaches, especially if you carry variants at other DAO positions.
Key References
Ayuso et al. identified three nonsynonymous DAO polymorphisms and showed their effect on serum enzyme activity
Maintz et al. association of AOC1 SNPs including rs10156191 with reduced serum DAO activity
Maintz & Novak comprehensive review of histamine and histamine intolerance mechanisms
Diamine oxidase rs10156191 and rs2052129 variants associated with migraine risk
Pilot study on prevalence of DAO gene variants in patients with histamine intolerance symptoms