The AOC1 Ser332Phe variant (rs1049742) is a key polymorphism affecting Diamine Oxidase (DAO) enzyme activity. This variant has been specifically linked to migraine susceptibility, making it particularly important for those who suffer from headaches triggered by certain foods or beverages.
Understanding Ser332Phe
The Ser332Phe variant involves an amino acid substitution at position 332 of the DAO enzyme:
- Serine (Ser): The ancestral, normal amino acid
- Phenylalanine (Phe): The variant amino acid that reduces enzyme efficiency
- Location: This change occurs in a region important for enzyme stability
Understanding Your Genotype
- G/G (Ser/Ser): Normal DAO activity at this position
- G/A (Ser/Phe): Heterozygous - moderately reduced DAO activity
- A/A (Phe/Phe): Homozygous variant - significantly reduced DAO activity
The Migraine Connection
Research has established a clear link between this variant and migraine susceptibility:
How Histamine Triggers Migraines
- Vasodilation: Histamine dilates blood vessels, including cerebral arteries
- Neuroinflammation: Histamine promotes inflammatory responses in neural tissue
- Trigeminal activation: Histamine can activate pain-sensing nerve fibers
- Mast cell involvement: Meningeal mast cells release histamine during migraine attacks
Research Findings
- Carriers of the A allele (Phe variant) show increased migraine risk
- The effect is dose-dependent - two copies confer higher risk than one
- Particularly relevant for migraines triggered by aged foods, wine, or fermented products
- May explain why some people get "wine headaches" while others don't
Food Triggers and This Variant
If you carry the Phe variant, these common migraine food triggers make more sense:
High-Histamine Migraine Triggers
- Red wine: Contains histamine plus blocks DAO - double impact
- Aged cheese: Parmesan, cheddar, and blue cheese are high in histamine
- Cured meats: Salami, pepperoni, and bacon
- Fermented soy: Soy sauce, miso, tempeh
- Vinegar: Found in many salad dressings and condiments
- Citrus: Triggers histamine release
- Chocolate: Both histamine content and release
Timing Patterns
- Migraine typically occurs 6-12 hours after histamine-rich meal
- Weekend migraines may relate to dining out or alcohol consumption
- Symptoms may worsen during allergy season (additional histamine load)
- Menstrual migraines can be exacerbated (estrogen increases histamine)
Management Strategies
Dietary Approaches
For carriers of the A allele:
- Keep a detailed food and headache diary to identify personal triggers
- Prioritize fresh over aged, fermented, or leftover foods
- If drinking wine, white wine is generally lower in histamine than red
- Choose fresh fish over canned or smoked varieties
- Opt for fresh meats rather than processed/cured options
DAO Support
- DAO supplements: Take before meals containing potential triggers
- Copper: Essential DAO cofactor (2mg daily typical recommendation)
- Vitamin B6: Supports enzyme function
- Vitamin C: Helps degrade histamine; may reduce frequency of migraines
Antihistamines
Some migraine sufferers find relief with:
- H1 blockers (cetirizine, loratadine) - may help if taken preventively
- H2 blockers (famotidine) - address gastric histamine
- Combination approaches targeting both H1 and H2 receptors
- Note: Work with your doctor - antihistamines are not standard migraine treatment
Compound Effects with Other Variants
This variant combines with other AOC1 SNPs:
- rs10156191 (Thr16Met): If you carry risk alleles at both positions, DAO activity is more significantly reduced
- rs2052129: Affects how much DAO is produced
- HNMT variants: If intracellular histamine degradation is also impaired, symptoms may be more severe
Prevalence
- European ancestry: A allele frequency approximately 10-15%
- Migraine association: Consistently replicated in European populations
- Other populations: Less studied, frequency varies
Beyond Migraines
While the migraine link is best studied, this variant may also influence:
- General histamine intolerance symptoms
- Digestive reactions to aged foods
- Skin reactions (flushing, hives) after eating
- Potential pregnancy complications (DAO is crucial during pregnancy)
Testing with NutraHacker
NutraHacker's Histamine Panel analyzes rs1049742 alongside other AOC1 variants and HNMT polymorphisms, providing a comprehensive view of your histamine metabolism genetics.
Frequently Asked Questions
Will avoiding histamine cure my migraines?
For some people with this variant, reducing histamine intake significantly decreases migraine frequency. However, migraines are multifactorial. A low-histamine diet is one tool that may help, especially if your migraines are food-triggered, but it may not eliminate all migraines.
Should I take DAO before drinking wine?
If you carry the A allele and notice wine triggers symptoms, taking DAO supplement 15-20 minutes before drinking may help. However, note that alcohol also directly inhibits DAO activity, so the benefit may be partial. Limiting wine consumption or choosing lower-histamine options may be more effective.
Can this variant affect my children?
Yes, if you carry the variant, there's a 50% chance of passing it to each child. If both parents carry it, children could inherit two copies. This is worth knowing if migraines run in your family.
References
- García-Martín E, et al. Diamine oxidase rs10156191 and rs1049742 variants are associated with the risk for migraine. Headache. 2015;55(2):276-286.
- Izquierdo-Casas J, et al. Low serum diamine oxidase (DAO) activity levels in patients with migraine. J Physiol Biochem. 2018;74(1):93-99.
- Maintz L, Novak N. Histamine and histamine intolerance. Am J Clin Nutr. 2007;85(5):1185-1196.