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DAO Origin

The main cause of enzymatic dysfunction has a genetic origin

Some people produce or possess an insufficient amount of diaminoxidase, which is why until recently several chronic pathologies, such as migraines, were considered hereditary, but in fact the hereditary factor is the enzymatic deficiency DAO.

Other causes may have their origin in taking some medications or the presence of other pathologies.

Genetic factors of DAO deficiency

Clearly, genetics is one of the factors that cause DAO deficiency. Several members of the same family may have this deficiency and suffer from multiple chronic pathologies that until recently were considered “hereditary”.

The genetic sequence of the DAO enzyme is found in a fragment located on chromosome 7 (7q34-q36) of the human genome and is composed of 5 exons and 4 introns. Many differences have been detected in the sequence of exons and introns of this gene, which is due to its genetic polymorphism.

In total, according to data from the National Center for Biotechnology Information (NCBI), there are 85 variants of a single nucleotide polymorphism (SNP) located and identified in the human gene of the DAO enzyme (AOC1). 17 of these SNPs are found in exons, 7 of which produce amino acid substitutions, which cause alterations in the metabolic capacity of the enzyme.

Of all the polymorphisms found in the AOC1 gene sequence, four of these polymorphisms produce low enzymatic activity in histamine metabolism: AOC1 gen: c.47C>T (rs10156191), c.995C>T (rs1049742), c.1990C>G (rs1049793), c.-691G>T (rs2052129) of the AOC1/ABP1 gene (responsible for the coding of the DAO enzyme)

The carriers of these SNPs exhibit lower DAO activity than non-carrier individuals, and differences in their levels of enzymatic activity are significant. Studies indicate that these polymorphisms related to a reduction in enzymatic function occur with a frequency of about 10%, especially affecting women.

Other amino acid replacement polymorphisms studied in the DAO gene do not show changes in its enzymatic activity. On the other hand, the p.T16M variant has been associated with an increased risk of hypersensitivity to NSAIDs (nonsteroidal anti-inflammatory drugs), being proposed as a biomarker of the clinical response to treatment with these drugs.

Pharmacological factors of DAO deficiency

„Natural food products are complex mixtures comprising chemicals, many of which do not yet have a defined role in human nutrition. Most of the substances without known nutritional function that exist in the products that we normally use do not seem to have harmful effects or may be present in such small quantities that they do not pose any danger to human health. However, in certain circumstances, these substances may have harmful effects to be taken into account. Some known substances contained in fermented foods are not toxic in normal subjects, but can become when the subject who consumes the food is under treatment with certain drugs that are able to alter their metabolism in the body. ” – 1981, Francisco Grande Covián, Spanish physician and researcher, founder and first president of the Spanish Nutrition Society.

There is a set of drugs involved in the deficiency or decreased activity of the enzyme diaminoxidase. They block or inhibit enzymes involved in the metabolism of histamine, especially DAO, or release endogenous histamine.

This is a significant risk, since over 90 drugs have been reported to be involved in influencing the metabolism of histamine, many of which are widely used. It has been estimated that 20% of the population consumes some of these drugs, which escalates the risk of suffering symptoms or pathologies derived from the accumulation of histamine.

In pathologies such as migraine, one effect of the consumption of these drugs can be the chronicization of symptoms, since most of the drugs prescribed to mitigate the effects of the disease are DAO inhibitors or drugs that release endogenous histamine.

Some of the reported drugs are: analgesics, antidepressants, antirheumatic, antiarrhythmic, anti-asthmatic, antihistamines and mucolytics, among others, the latter are used especially in children.

The main drugs with an inhibitory effect on the enzyme diaminoxidase (DAO): analgesics (metamizole, acetylsalicylic acid); antihistamines (diphenhydramine, climetidine, promethazine); anti-arrhythmics (propafenone, quinidine); anti-asthmatic (theophylline); antidepressants (amitryptillin, tranylcypromine); antihypertensives (dihydraazine, verapamil); antirheumatic (acemethacin); antiseptics (acriflavin); antituberculosis (isoniazid); bronchiolitis (aminophylline); cardiotonic (dobutamine); diuretics (amiloride, furosemide); expectorants (ambroxol, mucosan); mucolytics (acetylcysteine, frenacil fluimucil); antimalarial (chloroquine); antibiotics (clavulanic acid, isoniazid, augmentin, amoxiplus); antiemetics (metoclopramide, primperan); neuroleptics (haloperidol); procynthetic (metoclopramide); tranquilizers (diazepam); muscle relaxants (pacuronium).

* The most representative drugs with an endogenous histamine-releasing effect: analgesics (acetylsalicylic acid, meclofenamic acid, mefenamic acid, diclofenac, indomethacin, ketoprofen, meperidine, morphine or animal origin); anesthetics (thiopental, prolocaine, barbiturates); antitussives (codeine); cytostatics (cyclophosphamide); expectorants (ambroxol); mucolytics (acetylcysteine); muscle relaxants (D-tubocurarin, alcuroni); anti-inflammatory (naproxen).

Pathological factors of DAO deficiency

DAO deficiency appears to be more prevalent in the population with inflammatory bowel disease.

Ulcerative colitis and Crohn’s disease, pathologies that cause DAO deficiency, are always monitored when any clinical trial related to the endogenous accumulation of histamine develops. Normally, when distributing patients in the control group and patients with DAO deficiency, subjects with inflammatory bowel disease are usually excluded.

DAO deficiency has also been demonstrated in the postoperative intestine, as well as after chemotherapy treatments. Diaminoxidase is localized mainly in the small intestine and if the mucosa is reduced, implicitly the area of production of the enzyme also decreases.

In patients with Crohn’s disease (CD), where DAO activity in the intestines is reduced by 50% compared to the healthy population, a higher rate of recurrence of the disease after surgery was observed (mainly in those with low enzymatic activity). Therefore, DAO could be a useful marker to predict the risks of recurrence or complications in THE CD.


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