Oct 11, 2023
Histamine is a biogenic amine synthesized by l-histidine decarboxylase (HDC) containing pyridoxal phosphate (vitamin B-6) from the amino acid histidine. It is synthesized by mast cells, basophils, platelets, histaminergic neurons and enterochromaffin cells, where it is stored in intracellular vesicles and released upon stimulation (Maintz, L. & Novak, N., 2007). Histamine is involved in inflammatory and allergic responses, stomach acid secretion, memory and It is a neurotransmitter and neuromodulator that plays important roles in many biological reactions such as the regulation of learning. Defects in the histaminergic system have been linked to cognitive deficits in neurodegenerative diseases, including Alzheimer's disease and Down syndrome (Rutherford, K. et al., 2007). Histamine N-methyltransferase (HNMT), which is responsible for inactivating histamine in the brain, and diamine oxidase (DAO) enzyme, which is responsible for clearing extracellular histamine (Agúndez, G. et al., 2012).
Excess histamine resulting from histamine intolerance, an imbalance between accumulated histamine and histamine breakdown capacity, can cause a multitude of symptoms that mimic an allergic reaction (Maintz, L. & Novak, N. 2007).
What is the HDC Gene?
Histamine biosynthesis is carried out in a single step by the L-histidine decarboxylase enzyme (HDC) alone (Agúndez, G. et al., 2012). HDC is a member of the group II decarboxylase family, which encodes L-histidine decarboxylase and forms a homodimer that converts L-histidine to histamine in a pyridoxal phosphate-dependent manner (Xu, L. et al., 2022).
What is the HRH1 Gene?
HRH1 is one of four histamine receptors to which histamine is known to bind (Raje, N. et al., 2015). The human H1 receptor (HRH1) gene encodes HRH1, a protein receptor widely expressed on many different cell types in the body, including epithelial, vascular, brain, and immune cells. HRH1 binds to antihistamine drugs, and the resulting interaction blocks neuronal transmission in the histaminergic nervous system in the brain, activating downstream signaling that mediates sleep state. It is suggested that HRH1 gene polymorphism contributes to differences between patients' HRH1 gene expression levels (Li, J. et al., 2020).
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HISTAMINE SENSITIVITY |
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Genes |
rs |
Minor Allele |
Minor Allele Description |
Reference |
|
HDC |
rs2073440 |
C |
Increased relative risk for allergic rhinitis. |
|
|
HRH1 |
rs901865 |
A |
Increased relative risk for allergic asthma. |
|
The table above includes the genes and their polymorphisms involved in histamine metabolism. rs2073440 polymorphism increases the risk of developing rhinitis. This contributes to increasing evidence supporting an important role of genetic variations associated with histamine homeostasis in the risk of developing allergic diseases (Gervasini, G. et al., 2010).
Patients carrying the HRH1 -17C →T (rs901865) CC genotype are thought to have high levels of HRH1 transcripts, which triggers serious sedation side effects (Ding, F. et al., 2022). Additionally, the HRH1 -17 TT genotype has been shown to be associated with the allergic asthma phenotype in African American children (Anvari, S. et al., 2015). It has been observed that the CT+TT genotype increases the risk of allergic rhinitis in the -17C/T region of HRH1 (Chu, T. 2018).
REFERENCES
Anvari, S., Vyhlidal, C. A., Dai, H., & Jones, B. L. (2015). Genetic variation along the histamine pathway in children with allergic versus nonallergic asthma. American journal of respiratory cell and molecular biology, 53(6), 802-809.
Chu, T. (2018). Histamine H1 receptor gene polymorphism acts as a biological indicator of the prediction of therapeutic efficacy in patients with allergic rhinitis in the Chinese Han population. Journal of Cellular Biochemistry, 120(1), 164-170. https://doi.org/10.1002/jcb.27278
Ding, F., Lin, W., Chiu, K., Lin, W., Yang, C., Chang, C., Chang, J., Yang, F., & Chien, H. (2022). Combined impacts of histamine receptor H1 gene polymorphisms and an environmental carcinogen on the susceptibility to and progression of oral squamous cell carcinoma. Aging (Albany NY), 14(10), 4500-4512. https://doi.org/10.18632/aging.204089
Gervasini, G., G. Agúndez, J. A., García-Menaya, J., Martínez, C., Cordobés, C., Ayuso, P., Cornejo, J. A., Blanca, M., & García-Martín, E. (2010). Variability of the L-Histidine decarboxylase gene in allergic rhinitis. Allergy, 65(12), 1576-1584. https://doi.org/10.1111/j.1398-9995.2010.02425.x
Li, J., Chen, W., Peng, C., Zhu, W., Liu, Z., Zhang, W., Su, J., Li, J., & Chen, X. (2020). Human H1 receptor (HRH1) gene polymorphism is associated with the severity of side effects after desloratadine treatment in Chinese patients with chronic spontaneous uticaria. The Pharmacogenomics Journal, 20(1), 87-93. https://doi.org/10.1038/s41397-019-0094-0
Maintz, L., & Novak, N. (2007). Histamine and histamine intolerance. The American Journal of Clinical Nutrition, 85(5), 1185-1196. https://doi.org/10.1093/ajcn/85.5.1185
Raje, N., Vyhlidal, C. A., Dai, H., & Jones, B. L. (2015). Genetic variation within the histamine pathway among patients with asthma. The Journal of Asthma : Official Journal of the Association for the Care of Asthma, 52(4), 353. https://doi.org/10.3109/02770903.2014.973501
Rutherford, K., Parson, W. W., & Daggett, V. (2007). The Histamine N-Methyltransferase T105I Polymorphism Affects Active Site Structure and Dynamics. Biochemistry, 47(3), 893. https://doi.org/10.1021/bi701737f
Xu, L., Zhang, C., Zhong, M., Che, F., Guan, C., Zheng, X., & Liu, S. (2022). Role of histidine decarboxylase gene in the pathogenesis of Tourette syndrome. Brain and Behavior, 12(3). https://doi.org/10.1002/brb3.2511