rs1049793 — AOC1 (DAO) His645Asp

DAO His645Asp - The Third Piece of the DAO Puzzle

The His645Asp ¹¹ Histidine to aspartic acid at position 645 variant (rs1049793) is the third major functional variant in the AOC1 gene encoding diamine oxidase. This missense mutation replaces histidine with aspartic acid at position 645, which sits near the enzyme's catalytic domain.

The Mechanism

Position 645 is in a region of the DAO protein that contributes to substrate binding and catalytic turnover. The aspartic acid substitution ²² Histidine is positively charged at physiological pH while aspartic acid is negatively charged, dramatically changing local electrostatics (G allele) alters the local charge distribution, potentially affecting how efficiently the enzyme captures and degrades histamine molecules. Like the other DAO structural variants, this change reduces the enzyme's overall effectiveness. Ayuso et al.³³ Ayuso et al.
Ayuso P et al. Genetic variability of human diamine oxidase. Pharmacogenet Genomics, 2007 showed that heterozygous carriers had 34% reduced DAO activity and homozygous carriers had 49% reduced activity compared to non-carriers.

Combined DAO Status

The three major AOC1 variants (rs2052129, rs10156191, and rs1049793) together determine your overall DAO capacity. Research has demonstrated that these variants are partially independent - you can carry risk alleles at one position but not others. This means your total DAO function is best assessed by looking at all three variants together, rather than any single one in isolation.

Population Variation

This variant shows substantial population differences. The G allele frequency is approximately 30% in Europeans but reaches 49-54% in East Asian, South Asian, and African populations. This means reduced DAO activity at this position is more common in non-European populations.

Practical Guidance

The dietary strategies for managing reduced DAO function are consistent regardless of which specific variant is responsible: minimize high-histamine foods, prioritize freshness, and consider DAO supplementation with meals when consuming foods that are known histamine triggers. Importantly, histamine intolerance symptoms can wax and wane depending on your total histamine load ⁴⁴ Your histamine load is the sum of all histamine from diet, gut bacteria, allergic reactions, and internal production at any given time from food, environment, stress, and hormonal fluctuations.