Origin of DAO deficiency

The main reason for enzyme dysfunction has a genetic origin. This justifies the recent belief that chronic pathologies such as migraine are hereditary, when in fact the hereditary factor is DAO Deficiency.

Genetic factors of DAO Deficiency

The genetic sequence of the DAO enzyme in the human genome is found in a fragment located on chromosome 7 (7q34-q36) and is composed of 5 exons and 4 introns.

Many differences have been detected between the sequence of exons and introns of this gene that are due to its genetic polymorphism. In total, according to data from the National Center for Biotechnology Information (NCBI), there are 85 single nucleotide variants (SNPs) identified in the human DAO gene (AOC1). Seventeen of these SNPs are found in the exons, seven of
which produce amino acid substitutions and are therefore candidates for alterations in the enzyme’s metabolic capacity.

Of all the polymorphisms found in the AOC1 gene sequence, three of them (with reference: rs1015611, rs1049742 and rs1049793) produce low enzyme activity in histamine metabolism.

Classification of variants according to the recommendations of the American College of Medical Genetics and Genomics according to nomenclature of HGVS

Classification of variants according to the recommendations of the American College of Medical Genetics and Genomics according to nomenclature of HGVS



Carriers of these polymorphisms have lower diamine oxidase activity than non-carriers, and
the differences in activity levels are significant. Studies indicate that this type of polymorphism has a global prevalence of approximately 10%, affecting specially women.

Other studied amino acid substitution polymorphisms 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 (non-steroidal anti-inflammatory drugs), and has been proposed as a biomarker of clinical response to treatment with these drugs.

Pharmacological factors in DAO Deficiency

“Natural foods are very complex mixtures of chemical substances, many of which have no
known role in human nutrition. Most of these substances with unknown nutritional function do not seem to have harmful effects, or are present in such small quantities that does not represent any health hazard. But in some circumstances, they may exert harmful effects that need to be considered. Some known substances in fermented foods are not toxic in normal subjects, but may be toxic when the person who eats it is undergoing treatment with certain drugs capable of modifying their metabolism”.

– 1981, Francisco Grande Covián, Spanish physician and researcher. His main work was in the area of nutrition and biochemistry, being the founder and first president of the Spanish Society of Nutrition.

Several drugs are implicated in deficiency or low activity of the Diamine Oxidase (DAO) enzyme. They block or inhibit enzymes involved in histamine metabolism, especially DAO, or release endogenous histamine. This risk is of great importance, as about 90 implicated drugs have been published, some of them in very common use.

It has been estimated that 20% of the population are on ongoing treatment with these drugs, which increases the risk of suffering from symptoms or pathologies resulting from histamine accumulation.

In pathologies such as migraine, those treatments can cause chronic symptoms, as many of the drugs prescribed to alleviate the effects of migraine of the disease are DAO inhibitors or endogenous histamine releasers.

*Main drugs with inhibitory effect on Diamine Oxidase (DAO) enzyme: analgesics (metamizol, acetyl salicilic acid); antihistamines (diphenhidramine, climetidina, promethazine); anti-arrhytmics (propafenone, quinidine); anti-asthmatics (theophylline); antidepressants (amitryptiline, tranylcipromine); anti-hypertensives (dihidralazina, verapamil); atirheumatics (acemetacina); antiseptics (acriflavine); antituberculosis (isoniazid); bronchiolitics (aminophylline); cardiotonics (dobutamine); diuretics (amiloride, furosemide); expectorants (ambroxol, mucosan); mucolytics (acetylcisteine, fluimucil frenacil); antimalarials (chloroquine); antibiotics (clavulanic acid, isoniazida, augmentine, amoxiplus); antiemetics (metoclopramide, primperan); neuroleptics (haloperidol); procinetics (metoclopramide); tranquilizers (diazepam); muscle relaxants (pacuroni).
*Most representative drugs with liberating effect of endogenous histamine: analgesics (acetylsalicylic acid, meclofenamic acid, mefenamic acid, diclofenac, infometacina, ketoprofen, meperidine, morphine o animal origin); anestesics (thiopental, prolocaina, barbiturates); antitussives (codeine); cytostatics (cyclophosphamide); expectorants (ambroxol); mucolytics (acetilcysteine); muscle relaxants (D-tubocurarine, alcuroni); anti-inflammatory (naproxen).

Phatological factors of DAO deficiency

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

Ulcerative colitis and Crohn’s disease, pathologies that trigger DAO Deficiency, are always controlled for in any clinical study related to the accumulation of exogenous histamine. Normally, when allocating control groups and patients with DAO Deficiency, individuals with inflammatory bowel diseases are excluded.

DAO Deficiency has also been observed in the postoperative period following intestinal surgery, as well as after chemotherapy treatments. Diamine oxidase is mainly found in the intestine, therefore, if the mucosa is reduced or affected, the production area of the enzyme decreases.

In patients with Crohn’s disease (CD), where DAO activity in the intestinal mucosa is approximately 50% lower when compared to the healthy population, a higher rate of disease recurrence has been observed after surgery (especially in those with low enzyme activity). Therefore, DAO could be a useful marker to predict the risk of recurrence or complications in CD.

INFORMACIÓN COMPLETA SOBRE DÉFICIT DE DAO

Histamine in food

In addition to foods rich in histamine, high intakes of foods rich in other amines such as putrescine, cadaverine, b-phenylethylamine, tryptamine, serotonin, tyramine and agmatine can also lead

Diagnosis of DAO Deficiency

There are two ways in which the diagnosis can be made: the molecular genetic study of Diamine Oxidase (DAO) activity (AOC1-V) and/or the in vitro diagnostic test measuring

Origin of DAO deficiency

The main reason for enzyme dysfunction has a genetic origin.

This justifies the recent belief that chronic pathologies such as migraine are hereditary, when in fact the hereditary factor

Que es el Déficit de DAO
What is DAO Deficiency?

It is an alteration in the metabolism of food histamine that occurs when the activity of the Diamine Oxidase (DAO) enzyme is reduced. That is, when for certain

Histamine in food

In addition to foods rich in histamine, high intakes of foods rich in other amines such as putrescine, cadaverine, b-phenylethylamine, tryptamine, serotonin, tyramine and agmatine can also lead

Diagnosis of DAO Deficiency

There are two ways in which the diagnosis can be made: the molecular genetic study of Diamine Oxidase (DAO) activity (AOC1-V) and/or the in vitro diagnostic test measuring

Origin of DAO deficiency

The main reason for enzyme dysfunction has a genetic origin.

This justifies the recent belief that chronic pathologies such as migraine are hereditary, when in fact the hereditary factor

Que es el Déficit de DAO
What is DAO Deficiency?

It is an alteration in the metabolism of food histamine that occurs when the activity of the Diamine Oxidase (DAO) enzyme is reduced. That is, when for certain

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