MOLECULAR GENETIC STUDY OF DIAMINE OXIDASE (DAO) (AOC1-V) ACTIVITY
The genetic test developed by the Molecular Genetics Laboratory Genyca introduces the possibility of a non-invasive genetic study of the DAO activity. This is a test that performs a high sensitivity genotyping of the most relevant genetic variants of the AOC1 gene (DAO) on the basis of a saliva sample (buccal mucous).
Advantages of the genetic testing of the DAO activity:
- Comfortable: Can be done in house or in the pharmacy
- Easy: Obtaining saliva sample, painless and non-invasive
- Fast: Results in 7 days
- Unique: Aresult valid for life
- Innovative: At the forefront of technology
- Familiar: The result can indicate the likelihood of the existence of the gene variants associated with the DAO deficiency within the family
Introduction
DAO deficiency is characterized by an imbalance between the quantity of food histamine and the capacity of degradation of the same. The diamine oxidase (DAO/ABP1, Histaminase) is one of the two enzymes responsible for degrading the histamine. In particular, the DAO is responsible for deleting the extracellular histamine after the liberation of mediators (1). A malfunction of the catabolism of histamine results in the accumulation of high levels of this, causing multiple disorders, such as gastrointestinal symptoms, headache, migraine headaches, allergic rhinitis, atopic skin, wheezing, asthma-type and, less frequently, fibromyalgia, cardiovascular symptoms, hives, ADHD (Attention Deficit-Hyperactivity Disorder) (2).
Aplication of the test
Approximately 12% of the population suffers from Deficit of DAO, being more prevalent in women than in men(3). The deficit of DAO activity is associated with a lower capacity of degradation of histamine ingested in the diet.
One of the most recognized consequences of this metabolic disorder is migraine: despite its multifactorial etiology, evidenciadoque the deficit of DAO relates to the emergence of migraine (4-5). It has also been associated with the genetic variant p.T16M to an increased risk of hypersensitivity to NSAIDS ( nonsteroidal anti-inflammatory drugs), having been proposed as a biomarker of clinical response (6).
Description of the methodology
The DNA from the sample is obtained through automatic extraction, later performed a reaction of amplification by Polymerase Chain Reaction (PCR) multiplex of regions of interest of the AOC1 gene by using specific primers. The analysis of gene variants of interest is performed using SNPE Multiplex (Single Nucleotide First Extension) and subsequent analysis of fragments.
Gene variants incluided in the test
Serum levels of DAO expression present great interindividual variation. The gene that encodes the protein DAO/ABP1 is the AOC1 gene, for which have been described variants of type SNP (Single nucleotide variants), some of which are associated with reduced levels of DAO activity (7-8). In this test analyzes 3 allelic variants of AOC1:
Classification of variants according to the recommendations of the American College of Medical Genetics and Genomics according to nomenclature of HGVS
The presence or absence of a mutation does not exclude the possibility of another or others in regions not analyzed the gene in the patient or not detectable by the technique used, not being able, therefore, to exclude the possibility of disease.
Databases used:
– OMIM – Online Mendelian Inheritance in Man
– dbSNP – Database of Single Nucleotide Polymorphisms (12)
Conditions of test
- Sample of buccal mucosa in the swab, and completing the application form.
- Sample collection (simple transport, in stable support).
- TAT: 7 days.
- Obtaining the report of results through private access to the GENYCA`s platform for downloading .
Report of the results
Certain combinations of the variants analyzed are associated with a genetic deficiency of DAO activity. In the report of results are specified the variants detected in the patient, as well as the phenotypic interpretation of DAO reduction of activity based on the results obtained.
Quality control
GENYCA is a laboratory certified by the UNE-EN-ISO 9001:2015, which performs genetic analysis through procedures and validated protocols and recommended by the European Network of Quality of Molecular Genetics (EMQN). Our analyzes are validated according to international guidelines (9) and comply with all technical and methodological requirements listed in the accreditation standard UNE-EN-ISO 15189: 2012, and participates regularly in external quality controls.
References
1. García-Martín et al. Histamine pharmacogenomics. Pharmacogenomics 2009; 10(5):867-883.
2. Maintz et al. Histamine and histamine intolerance. Am J Clin Nutr 2007; 85:1185-1196.
3. Jarisch et al. Histamin-Intoleranz. Histamin und Seekrankheit, 2 edn. Stuttgart, Germany: Georg Thieme Verlag KG, 2004.
4. Izquierdo-Casas et al. Low serum diamine oxidase (DAO) activity levels in patients with migraine. J Physiol Biochem 2018;74(1):93-99.
5. García-Martín et al. Diamine oxidase rs10156191 and rs2052129 variants are associated with the risk for migraine. Headache 2015;55(2):276-86.
6. Agúndez et al. The Diamine Oxidase gene is associated with hypersensitivity response to non-steroidal anti-inflammatory drugs. PLOS 2012; 7(11):e47571.
7. Ayuso et al. Genetic variability of human diamine oxidase: occurrence of three nonsynonymous polymorphisms and study of their effect on serum enzyme activity. Pharmacogenet Genomics 2007; 17(9):687-93.
8. Maintz et al. Association of single nucleotide polymorphisms in the diamine oxidase gene with diamine oxidase serum activities. Allergy 2001; 66:893-902.
9. Mattocks et al. A standardized framework for the validation and verification of clinical molecular genetic tests. Eur J Hum Genet. 2010 Dec;18(12):1276-88. doi: 10.1038/ejhg.2010.101.
10. Richards et al. (2015). Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med 17:405–24.
11. Den Dunnen et al. (2016). HGVS recommendations for the description of sequence variants: 2016 update. Hum.Mutat. 25: 37: 564-569.
12. Sherry et al. (2001). dbSNP: the NCBI database of genetic variation. Nucleic Acids Res 29:308–11.
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