Association of single nucleotide polymorphisms in the diamine oxidase gene with diamine oxidase serum activities

Maintz, Laura; Yu, Chunfeng; Rodríguez, Elke; Baurecht, Hansjörg; Bieber, Thomas; Illig, Thomas; Weidinger, Stephan; Novak, Natalija

doi:10.1111/j.1398-9995.2011.02548.x

Cited by 71 publications

(93 citation statements)

References 30 publications

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“…Previous investigations of the impact of histamine degrading enzyme genotype have revealed functional differences in enzyme kinetics and alterations in enzyme function. ABP1 4107 SNPs, which are associated with increased histamine response (increased Emax) in our study, are reported to result in missense mutations and decreased enzyme activity (Ayuso et al, 2007; Maintz et al, 2011). This previous in-vitro work lends biological plausibility to our findings in children with asthma.…”

Section: Discussionsupporting

confidence: 48%

Genetic Variation in the Histamine Production, Response, and Degradation Pathway Is Associated with Histamine Pharmacodynamic Response in Children with Asthma

et al. 2017

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Introduction: There is growing knowledge of the wide ranging effects of histamine throughout the body therefore it is important to better understand the effects of this amine in patients with asthma. We aimed to explore the association between histamine pharmacodynamic (PD) response and genetic variation in the histamine pathway in children with asthma.Methods: Histamine Iontophoresis with Laser Doppler Monitoring (HILD) was performed in children with asthma and estimates for area under the effect curve (AUEC), maximal response over baseline (Emax), and time of Emax (Tmax) were calculated using non-compartmental analysis and non-linear mixed-effects model with a linked effect PK/PD model. DNA isolation and genotyping were performed among participants to detect known single nucleotide polymorphisms (SNPs) (n = 10) among genes (HDC, HNMT, ABP1, HRH1, HRH4) within the histamine pathway. General linear model was used to identify associations between histamine related genetic variants and measured histamine PD response parameters.Results: Genotyping and HILD response profiles were completed for 163 children. ABP1 47 C/T, ABP1 4107, and HNMT-1639 C/Twere associated with Emax (ABP1 47 CC genotype mean Emax 167.21 vs. CT/TT genotype mean Emax 139.20, p = 0.04; ABP1 4107 CC genotype mean Emax 141.72 vs. CG/GG genotype mean Emax 156.09, p = 0.005; HNMT-1639 CC genotype mean Emax 132.62 vs. CT/TT genotype mean Emax 155.3, p = 0.02). In a stratified analysis among African American children only, ABP1 and HNMT SNPs were also associated with PD response; HRH4 413 CC genotype was associated with lower Emax, p = 0.009.Conclusions: We show for the first time that histamine pathway genetic variation is associated with measureable changes in histamine response in children with asthma. The variability in histamine response and impact of histamine pathway genotype is important to further explore in patients with asthma so as to improve disease phenotyping leading to more personalized treatments.

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Section: Discussionsupporting

confidence: 48%

Genetic Variation in the Histamine Production, Response, and Degradation Pathway Is Associated with Histamine Pharmacodynamic Response in Children with Asthma

et al. 2017

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“…Various single nucleotide polymorphisms (SNPs) in the DAO gene have been identified 14 and shown to be associated with DAO serum activity 15 and with hypersensitivity to non-steroidal anti-inflammatory drugs (NSAIDs). 16 Due to the multifaceted nature of histamine intolerance symptoms, the prevalence of this syndrome has long been underestimated and its symptoms misinterpreted.…”

Section: Introductionmentioning

confidence: 99%

Serum diamine oxidase activity in patients with histamine intolerance

Manzotti

Breda²,

Gioacchino

et al. 2015

Int J Immunopathol Pharmacol

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Introduction: Intolerance to various foods, excluding bona fide coeliac disease and lactose intolerance, represents a growing cause of patient visits to allergy clinics.Histamine intolerance is a long-known, multifaceted clinical condition triggered by histamine-rich foods and alcohol and/or by drugs that liberate histamine or block diamine oxidase (DAO), the main enzyme involved in the metabolism of ingested histamine. Histamine limitation diets impose complex, non-standardized restrictions that may severely impact the quality of life of patients. Methods: We retrospectively evaluated 14 patients who visited allergy outpatient facilities in northern Italy with a negative diagnosis for IgE-mediated food hypersensitivity, coeliac disease, conditions related to gastric hypersecretion, and systemic nickel hypersensitivity, and who previously underwent a histamine limitation diet with benefits for their main symptoms. Serum diamine oxidase levels and the clinical response to diamine oxidase supplementation were investigated. Results: We found that 10 out of 14 patients had serum DAO activity <10 U/mL, which was the threshold suggested as a cutoff for probable histamine intolerance. Moreover, 13 out of 14 patients subjectively reported a benefit in at least one of the disturbances related to food intolerances following diamine oxidase supplementation. The mean value (± SD) of diamine oxidase activity in the cohort of patients with histamine intolerance symptoms was 7.04 ± 6.90 U/mL compared to 39.50 ± 18.16 U/mL in 34 healthy controls (P = 0.0031). Conclusion:In patients with symptoms triggered by histamine-rich food, measuring the serum diamine oxidase activity can help identify subjects who can benefit from a histamine limitation diet and/or diamine oxidase supplementation.Properly designed, controlled studies investigating histamine intolerance that include histamine provocation are indispensable for providing insights into the area of food intolerances, which are currently primarily managed with nonscientific approaches in Italy.

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“…In mammals, DAO is mainly expressed at the level of the intestinal villi, in accordance with a peak enzymatic efficiency at pH 6.3 [6, 7]. Circulating levels of DAO may reflect DAO expression in the gastrointestinal tract [8]. Imbalances in the control of histamine levels due to inefficient DAO-related histamine clearance may lead to histamine accumulation and to the development of undesired histamine-related manifestations such as urticaria, accelerated gastrointestinal transit, or headache [2].…”

Section: Introductionmentioning

confidence: 99%

Diamine Oxidase Supplementation in Chronic Spontaneous Urticaria: A Randomized, Double-Blind Placebo-Controlled Study

Yacoub¹,

Ramirez²,

Berti³

et al. 2018

Int Arch Allergy Immunol

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Introduction: Diamine oxidase (DAO) catabolizes and inactivates histamine, a key player in a wide range of invalidating conditions, such as migraine and chronic spontaneous urticaria (CSU). The highest expression of DAO occurs in the gastrointestinal tract, possibly to control the burden of histamine intake from food. Methods: Here, we tested the hypothesis that a 30-day oral supplementation with DAO (1 capsule b.i.d., 15 min before a meal) could reduce the severity of CSU as estimated by the 7-Day Urticaria Activity Score (UAS-7). The study was designed as a double-blind, placebo-controlled, crossover investigation of 22 patients with CSU incompletely controlled by first-line antihistamine therapy. Results: Twenty patients completed the study. Supplemental therapy with DAO caused a 3.8 ± 1.2 point mean ± SEM UAS-7 score reduction in patients with low serum DAO levels at time 0 (p = 0.041 compared to placebo). The degree of UAS-7 improvement was inversely correlated with the levels of basal DAO (p = 0.019). Patients receiving DAO supplementation were able to slightly reduce their daily antihistamine dose (p = 0.049). Conclusion: These data suggest that DAO may be involved in the pathogenic cascade of CSU and that DAO supplementation could be effective for symptom relief in patients with low DAO levels in serum.

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Association of single nucleotide polymorphisms in the diamine oxidase gene with diamine oxidase serum activities

Abstract: DAO gene variants strongly influence DAO expression and activity but alone are not sufficient to fully effectuate the potentially associated disease state of HIT, suggesting an interplay of genetic and environmental factors.

Cited by 71 publications

References 30 publications

Genetic Variation in the Histamine Production, Response, and Degradation Pathway Is Associated with Histamine Pharmacodynamic Response in Children with Asthma

Genetic Variation in the Histamine Production, Response, and Degradation Pathway Is Associated with Histamine Pharmacodynamic Response in Children with Asthma

Serum diamine oxidase activity in patients with histamine intolerance

Diamine Oxidase Supplementation in Chronic Spontaneous Urticaria: A Randomized, Double-Blind Placebo-Controlled Study

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