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Origin of DAO Deficiency

The main cause of the enzymatic dysfunction has a genetic origin.


Some people have or produce few Diamine Oxidase, this is reason why until recently several chronic pathologies, such as migraine, were believed to be hereditary, when in fact, the hereditary factor is the deficiency of DAO.

Other causes may have their origin in drugs or other pathologies.

 

Genetic factors

Clearly, genetics is one of the factors that causes DAO Deficiency. In the same family unit, its members share this deficiency and many chronic pathologies that until now were considered "hereditary".

The enzyme alteration or what the cause of the genetic deficiency is, has not been properly studied yet, but it may be related to the genetic polymorphism of a Dao enzyme nucleotide. According to the National Center for Biotechnology Information (NCBI) data, the gene encoding DAO is a polymorphic gene. The genetic sequence of DAO is found in a fragment located on chromosome 7 (7q34-q36) of the human genome and it consists of 5 exons and 4 introns.

Many differences between the sequence of exons and introns of this gene, due to their genetic polymorphism, have been found. In total, there are 85 single nucleotide polymorphisms located and identified in the DAO human gene (17 in exons, of which 7 have substitution of amino acids).

Among all polymorphisms found in DAO sequence, it has been proved that only one of the 7 polymorphisms, (with reference rs1049793) located in the third exon, has relation with low DAO activity.

Carriers of this polymorphism, present lower DAO activity than controls with significant effect. Preliminary studies suggest that this polymorphism has an overall prevalence close to 0.30% (30% of mutated alleles).

Other studied polymorphisms of the same type of substitution of amino acids, do not show changes in enzyme DAO activity.



Pharmacological factors

"Natural food products are complex mixtures comprising chemical substances, many of which have not a defined role in human nutrition yet. Most substances without known nutritional function which exist in products that we normally use do not seem to have harmful effects, or they may be present in such small amounts that they do not represent any danger to human health. Nevertheless, in some circumstances these substances may have damaging effects that must be taken into account. Some known substances found in fermented foods are not toxic in normal subjects, but they may be when the subject consuming the food is under treatment with certain drugs that are able to modify their metabolism within the organism."
Francisco GRANDE COVIÁN, 1981




There is set of drugs involved in the deficiency or low activity of Diamine Oxidase enzyme. They block or inhibit enzymes involved in the metabilization of histamine, DAO in particular, or release endogenous histamine. This is a very significant risk, as over 90 drugs have been reported to be involved, many of them widely used. It has been estimated that 20% of the population use some of these drugs, increasing the risk of suffering symptoms or pathologies derived from histamine accumulation.

In pathologies such as migraine, an effect of the consumption of these drugs may be the chronification of symptoms, as most drugs prescribed to palliate the effects of the illness are DAO inhibitors or endogenous histamine-releasing drugs.

Some of the reported drugs are: analgesics, antidepressants, antirheumatics, antiarrhythmics, antiarrhythmics, antihistamines and mucolytics, among others, being these last ones used especially in children.



Fármacos más representativos con efecto inhibidor sobre la enzima metabolizadora de la histamina, la DAOtabla1  Most representative drugs liberating effect of endogenous histaminetabla2

Pathological factors

DAO Deficiency seems to be more prevalent in population with inflammatory bowel diseases. It has been mainly detected in patients with colon cancer.


Ulcerative colitis and Crohn disease, pathologies with DAO Deficiency, are always monitored when developing any study related to endogenous histamine accumulation. Normally, when distributing patients in controls and patients with DAO Deficiency, those subjects with inflammatory bowel diseases are usually excluded.


DAO Deficiency has also been demonstrated in postoperative bowel. Diamine Oxidase is mainly located in the small bowel and if part of the mucosa decreases, so does the enzyme production area.


In Crohn's disease patients, where DAO activity in the intestinal bowel is reduced by 50% regarding healthy population, a higher recurrence rate of the disease has been observed after surgery (mainly in those with low enzyme activity). Therefore, DAO is said to be a useful marker to foresee recurrence risks or complications in CD.

The main cause of the enzymatic dysfunction has a genetic origin.

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