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Pharmacogenetics of H1 antihistamines in Iranian patients with chronic Idiopathic urticaria
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Ebrahim Mohammadi   , Rasoul Nasiri Kalmarzi , Sedigh Rostamian , Fakhredin Karimpour , Taraneh Rostami Jalilian , Ramin Lotfi , Fatemeh Zamani , Abbas Aghaei |
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Abstract: (262 Views) |
Introduction: Previous studies have suggested that variations in histamine-related genes may affect the severity of allergic diseases. The aim of the present study is to investigate the possible association between functional polymorphisms of antihistamine pharmacokinetics-related genes (diamine oxidase, ABP1 rs1049793, C47T, and histamine N-methyltransferase, HNMT rs11558538, C314T) and pharmacodynamics-related genes (histamine receptor H4, HRH4 rs11662595, A617G, and 11685084, C413T) in Iranian patients with chronic idiopathic urticaria (CIU).
Methods and Materials: One hundred and twenty-six patients with confirmed CIU were recruited for this study. DNA was extracted from peripheral blood and genotyping of ABP1, HNMT, and HRH4 genes was determined by a new PCR-RFLP method. The urticaria activity score (UAS) in the 1st and 12th weeks after treatment and the side effects of antihistamine drugs were determined by a clinician in clinic. IgE and D-dimer serum levels were measured by ELISA method.
Results: The frequencies of rs11558538, rs1049793, rs11662595, and 11685084 polymorphisms in patients participating in the study were calculated as 55.5%, 26.2%, 17.7%, and 16.1%, respectively. According to the follow-up during 12 weeks, responses to antihistamines (based on UAS) were significantly lower in the heterozygous genotypes of the HNMT and ABP1 genes compared to wild-type harbors of these genes. Furthermore, patients who had the variant alleles of all three genes showed higher serum levels of D-dimer compared to the patients with wild-type alleles. More side effects were statistically recorded for patients with ABP1 and HNMT but not for HRH4 variants. No statistical differences in serum IgE levels were detected among different patient groups.
Conclusions: We show for the first time that genetic variations in histamine-related genes are associated with responses to H1 antihistamine drugs in chronic urticaria. The results of our study may be applied to improving antihistamine treatment and personalizing therapy in patients with chronic urticaria.
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| Keywords: Chronic spontaneous urticaria (CSU), H1 antihistamines, Diamine oxidase (ABP1), histamine N-methyltransferase (HNMT), Histamine receptor H4 (HRH4), Urticaria activity score (UAS) |
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Full-Text [PDF 265 kb]
(42 Downloads)
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Type of Study: Research |
Subject:
General
Received: 2023/12/30 | Accepted: 2023/08/23 | Published: 2023/08/23
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