Polymorphisms of histamine‐metabolizing enzymes and clinical manifestations of asthma and allergic rhinitis

García‐Martín, Elena; García-Menaya, Jesús Miguel; Sánchez, Blanca de Vega; Martı́nez, Carmen; Rosendo, Rosana Araújo; Agúndez, José A. G.

doi:10.1111/j.1365-2222.2007.02769.x

Cited by 60 publications

(57 citation statements)

References 37 publications

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“…Polymorphisms in the HDC and SLC22A3 genes influenced the risk of both rhinitis and asthma [19]. The association of asthma with HNMT SNP could not be observed in two Caucasian (Spanish and German) and an Indian population [20,21,22]. HNMT gene polymorphism did not influence the endophenotypes of asthma in the German group either [21].…”

Section: Discussionmentioning

confidence: 99%

Asthma Endophenotypes and Polymorphisms in the Histamine Receptor HRH4 Gene

Simon

Semsei²,

Ungvári³

et al. 2012

Int Arch Allergy Immunol

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Background: Histamine as an inflammatory mediator plays an important role in chronic allergic and asthmatic conditions. However, the role of genetic polymorphisms of the histamine receptor HRH4 (histamine receptor H4) gene in asthma susceptibility and endophenotypes has not been studied yet. Our aim was to investigate the possible association between single nucleotide polymorphisms (SNPs) in the HRH4 gene and asthma or some endophenotypes of asthma. Methods: Twenty-one SNPs of the HRH4 gene were genotyped in 313 asthmatic patients and 360 controls using Sequenom® iPLEX® Gold Genotyping Technology. Results: Genotype distribution of three HRH4 SNPs, namely rs17187619 [p = 0.002; odds ratio, OR (95% confidence interval, CI) = 2.4 (4.1–1.4)], rs527790 [p = 0.0002; OR (95% CI) = 3.3 (6.1–1.8)] and rs487202 [p = 0.00007; OR (95% CI) = 3.5 (6.6–1.9)] differed significantly between patients with or without infection-induced asthma. Haplotypes, which included the rs4800573–rs527790 CC allele combination, were found to be associated with infection-induced asthma [p = 0.0009, OR (95% CI) = 0.5 (0.4–0.8)]. The rs487202–rs574913 CA haplotype was more frequent among patients with infection-induced asthma [p = 0.0006, OR (95% CI) = 1.9 (1.3–2.6)]. None of the SNPs contributed directly to the risk of asthma. Conclusions: Our results suggest that genetic variation in the HRH4 gene might influence the pathogenesis of infection-induced asthma.

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Section: Discussionmentioning

confidence: 99%

Asthma Endophenotypes and Polymorphisms in the Histamine Receptor HRH4 Gene

Simon

Semsei²,

Ungvári³

et al. 2012

Int Arch Allergy Immunol

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“…Garcia-Martin, et al reported an association between ABP1 4107C/G (His645Asp) and allergic asthma and/or allergic rhinitis among 270 Caucasians and 295 unrelated controls [37]. The allergic phenotype in their study was well-defined by clinical history and environmental allergy skin prick testing.…”

Section: Discussionmentioning

confidence: 91%

“…Conflicting reports exist among various ethnic groups and asthma phenotypes in relation to the HNMT 314 SNP and asthma [36,37,40,41]. Sasaki, et al also did not find a relationship between the SNP and allergic asthma in the Japanese cohort [40].…”

Section: Discussionmentioning

confidence: 92%

“…Although the functional significance of many of these SNPs is unknown, several studies have been conducted to explore potential associations between histamine related genes and asthma and allergic disease [6,17,[33][34][35][36][37][38][39][40][41][42][43]. We have previously reported that the HRH1 gene was more highly expressed in buccal tissue from those with asthma compared to those without asthma [44].…”

Section: Introductionmentioning

confidence: 99%

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Genetic Variation Along The Histamine Pathway In Children With Allergic Vs. Non-Allergic Asthma

Anvari

Vyhlidal

Rezaiekhaligh

et al. 2014

Journal of Allergy and Clinical Immunology

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ABSTRACT:Rationale: Previous studies have suggested that antihistamines may be therapeutic in some patients with asthma. Variation in genes along the histamine production, response, and degradation pathway may be important in predicting response to antihistamines. We hypothesize that genetic variation in genes of the histamine pathway differs between children with allergic versus non-allergic asthma.Methods: Children 7-18 years of age (n=118) with asthma participated in this IRB-approved protocol and were classified as allergic (N = 68) or non-allergic (N = 50) based on allergy skin testing. DNA isolation and genotyping were performed for 10 SNPs within 4 genes (HDC, HNMT, ABP1, HRH1, HRH4) within the histamine pathway. Chi Square tests were used to test for associations between genotypes and allergic or non-allergic asthma among participants.Significance was determined by p <0.05. Results:We observed differences in genotype frequency between participants with allergic versus non-allergic asthma for 2 SNPs: HNMT-1639(rs6430764) (31% allergic with TT vs. 14% non-allergic with TT, p=0.04) and HNMT -464 (rs2071048) genotype (33% allergic with TT vs.12% non-allergic with TT, p=0.03) after controlling for race. Differences in genotype frequency were also observed between allergic and non-allergic phenotypes in stratified analyses among African Americans. Conclusion:Genetic variants within the histamine pathway appear to be associated with an allergic versus non-allergic asthma phenotype. Further studies are needed to validate our findings in a larger cohort. There is also the need to determine the functional significance of identified SNPs and their impact on antihistamine response in patients with asthma and allergic disease. iv ACKNOWLEDGMENTS:

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“…In addition, studies have indicated that the number of times patients were awakened by asthma during the night is also an important factor that evaluates the efficacy of the childhood asthma treatment (45,46). Furthermore, contraction of the airways is another factor to evaluate the extent of capillary bronchitis, which may be an early signal of bronchial asthma in children (47,48).…”

Section: Discussionmentioning

confidence: 99%

Clinical efficacy of recombinant human latrophilin 3 antibody in the treatment of pediatric asthma

Liu¹,

Zhang²,

Liu³

2017

Exp Ther Med

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Abstract. Pediatric asthma is a chronic pulmonary inflammatory disease featuring hypersecretion of mucus and inflammation in the airway, resulting in dysfunction of the airway smooth muscle. Previous evidence demonstrated that latrophilins, a novel family of receptors, present a beneficial effect on airway smooth muscle cells. In the present study, the therapeutic effects of recombinant human latrophilin 3 (rhLPHN3) antibody (Ab) in patients with pediatric asthma were investigated, and the molecular mechanism underlying the function of LPHN3 in the treatment of asthma in clinical practice was examined. A total of 342 pediatric asthma cases were recruited and randomly divided into three groups, receiving treatment with rhLPHN3 Ab (n=134), salbutamol (n=108) or montelukast (n=100) by nasal aerosolization. Each group received the respective clinically tested dose for 16 weeks. Inflammatory factors interleukin (IL)-10, IL-17, IL-4, matrix metallopeptidase-9 (MMP-9), interferon-γ (IFN-γ) and transforming growth factor-β (TGF-β) levels in peripheral blood mononuclear cells were analyzed prior to and post treatment. The clinical outcomes revealed that pathological alterations were significantly improved following treatment with rhLPHN3 Ab for patients with pediatric asthma when compared with those receiving salbutamol and montelukast. It was also observed that rhLPHN3 Ab downregulated the plasma concentration levels of IL-10, IL-17, IL-4 and MMP-9, and upregulated IFN-γ and TGF-β levels in the three groups. In addition, clinical data demonstrated that rhLPHN3 Ab significantly promoted E-selectin and mucin 5AC expression, as well as improved the activation of nuclear factor (NF)-κB p65 DNA binding activity and the phosphorylation levels of protein kinase A. Furthermore, rhLPHN3 Ab markedly improved adhesion and proliferation of airway smooth muscle cells, which led to promotion of the contraction of these cells.In conclusion, these clinical data suggest that rhLPHN3 Ab serves an important role in the inhibition of inflammatory mediators through downregulation of NF-κB signaling pathway, which contributes to airway remodeling and bronchodilation in patients with pediatric asthma.

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Polymorphisms of histamine‐metabolizing enzymes and clinical manifestations of asthma and allergic rhinitis

Abstract: There is a lack of association between the allelic variants studied and the risk of developing allergic asthma and rhinitis. However, patients carrying the His645Asp polymorphism of ABP1 are more prone to developing symptoms with lower IgE levels.

Cited by 60 publications

References 37 publications

Asthma Endophenotypes and Polymorphisms in the Histamine Receptor <b><i>HRH4</i></b> Gene

Asthma Endophenotypes and Polymorphisms in the Histamine Receptor <b><i>HRH4</i></b> Gene

Genetic Variation Along The Histamine Pathway In Children With Allergic Vs. Non-Allergic Asthma

Clinical efficacy of recombinant human latrophilin 3 antibody in the treatment of pediatric asthma

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