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Start Over Author "Torres MJ" Topic amine oxidase (copper-containing) Journal plos one
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1. The diamine oxidase gene is associated with hypersensitivity response to non-steroidal anti-inflammatory drugs.

Author

Agúndez JA, Ayuso P, Cornejo-García JA, Blanca M, Torres MJ, Doña I, Salas M, Blanca-López N, Canto G, Rondon C, Campo P, Laguna JJ, Fernández J, Martínez C, and García-Martín E

Subjects
Adolescent, Adult, Aged, Aged, 80 and over, Alleles, Amine Oxidase (Copper-Containing) immunology, Case-Control Studies, Child, Child, Preschool, Drug Hypersensitivity immunology, Female, Gene Frequency, Genotype, Humans, Immunoglobulin E immunology, Male, Middle Aged, Polymorphism, Single Nucleotide, Young Adult, Amine Oxidase (Copper-Containing) genetics, Anti-Inflammatory Agents, Non-Steroidal adverse effects, Drug Hypersensitivity genetics
Abstract

Unlabelled: Non-steroidal anti-inflammatory drugs (NSAIDs) are the drugs most frequently involved in hypersensitivity drug reactions. Histamine is released in the allergic response to NSAIDs and is responsible for some of the clinical symptoms. The aim of this study is to analyze clinical association of functional polymorphisms in the genes coding for enzymes involved in histamine homeostasis with hypersensitivity response to NSAIDs. We studied a cohort of 442 unrelated Caucasian patients with hypersensitivity to NSAIDs. Patients who experienced three or more episodes with two or more different NSAIDs were included. If this requirement was not met diagnosis was established by challenge. A total of 414 healthy unrelated controls ethnically matched with patients and from the same geographic area were recruited. Analyses of the SNPs rs17740607, rs2073440, rs1801105, rs2052129, rs10156191, rs1049742 and rs1049793 in the HDC, HNMT and DAO genes were carried out by means of TaqMan assays. The detrimental DAO 16 Met allele (rs10156191), which causes decreased metabolic capacity, is overrepresented among patients with crossed-hypersensitivity to NSAIDs with an OR  = 1.7 (95% CI  = 1.3-2.1; Pc  = 0.0003) with a gene-dose effect (P = 0.0001). The association was replicated in two populations from different geographic areas (Pc  = 0.008 and Pc  = 0.004, respectively)., Conclusions and Implications: The DAO polymorphism rs10156191 which causes impaired metabolism of circulating histamine is associated with the clinical response in crossed-hypersensitivity to NSAIDs and could be used as a biomarker of response.

Published
2012
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2. The diamine oxidase gene is associated with hypersensitivity response to non-steroidal anti-inflammatory drugs

Author

Elena García-Martín, José A. G. Agúndez, Gabriela Canto, Carmen Martínez, María L. Salas, Natalia Blanca-López, Paloma Campo, Javier Fernández, Jose A. Cornejo-Garcia, Inmaculada Doña, María José Torres, Carmen Rondon, Jose Julio Laguna, Miguel Blanca, Pedro Ayuso, [Agúndez,JAG, Martínez,C] Departamento de Farmacología, Universidad de Extremadura, Cáceres, Spain. [Ayuso,P, García-Martín,E] Departamento de Bioquímica y Biología Molecular y Genética, Universidad de Extremadura, Cáceres, Spain. [Cornejo-García,JA] Laboratorio de Investigación, Fundación IMABIS, Málaga, Spain. [Blanca,M, Torres,MJ, Doña,I, Salas,M, Rondon,C, Campo,P] Servicio de Alergologia, Hospital Carlos Haya, Málaga, Spain. [Blanca-López,N, Canto,G, Servicio de Alergologia, Hospital Infanta Leonor, Madrid, Spain. [Laguna, JL] Servicio de Alergologia, Hospital Cruz Roja, Madrid, Spain. [Fernández,J] Servicio de Alergologia, Hospital San Juan, Alicante, Spain., and FIS PS09/00943, PS09/00469, and RETICS RD07/0064/0016 from Fondo de Investigacio´n Sanitaria, Instituto de Salud Carlos III, Spain, and GR10068 from Junta de Extremadura, Spain. Financed in part with FEDER funds from the European Union

Subjects
Male, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Globulins::Serum Globulins::Immunoglobulins::Antibodies::Immunoglobulin Isotypes::Immunoglobulin E [Medical Subject Headings], Named Groups::Persons::Age Groups::Adult::Aged::Aged, 80 and over [Medical Subject Headings], Named Groups::Persons::Age Groups::Adult::Middle Aged [Medical Subject Headings], Pharmacology, Immunoglobulin E, medicine.disease_cause, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], chemistry.chemical_compound, Gene Frequency, Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Oxidoreductases::Oxidoreductases Acting on CH-NH2 Group Donors [Medical Subject Headings], Hipersensibilidad medicamentosa, Child, Aged, 80 and over, Multidisciplinary, Estudios de casos y controles, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Case-Control Studies [Medical Subject Headings], Named Groups::Persons::Age Groups::Child::Child, Preschool [Medical Subject Headings], biology, Allergy and Hypersensitivity, Anti-Inflammatory Agents, Non-Steroidal, Middle Aged, Named Groups::Persons::Age Groups::Adolescent [Medical Subject Headings], Child, Preschool, Allergic response, Medicine, Female, Phenomena and Processes::Genetic Phenomena::Genotype [Medical Subject Headings], Amine Oxidase (Copper-Containing), Diamine oxidase, Histamine, Research Article, Adult, Drugs and Devices, Named Groups::Persons::Age Groups::Adult::Young Adult [Medical Subject Headings], Adolescent, Genotype, Frecuencia de los Genes, Science, Immunology, Check Tags::Male [Medical Subject Headings], Single-nucleotide polymorphism, Polymorphism, Single Nucleotide, Drug Hypersensitivity, Young Adult, Adverse Reactions, Named Groups::Persons::Age Groups::Adult [Medical Subject Headings], medicine, Genetics, Humans, Named Groups::Persons::Age Groups::Adult::Aged [Medical Subject Headings], Allele frequency, Biology, Phenomena and Processes::Genetic Phenomena::Genetic Structures::Genome::Genome Components::Genes::Alleles [Medical Subject Headings], Named Groups::Persons::Age Groups::Child [Medical Subject Headings], Alleles, Aged, Clinical Genetics, iinmunoglobulina E, Evolutionary Biology, Phenomena and Processes::Genetic Phenomena::Genetic Variation::Polymorphism, Genetic::Polymorphism, Single Nucleotide [Medical Subject Headings], Population Biology, Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Anti-Inflammatory Agents::Anti-Inflammatory Agents, Non-Steroidal [Medical Subject Headings], business.industry, Haplotype, Case-control study, Personalized Medicine, Check Tags::Female [Medical Subject Headings], chemistry, Pharmacogenetics, Case-Control Studies, biology.protein, Genetic Polymorphism, Diseases::Immune System Diseases::Hypersensitivity::Drug Hypersensitivity [Medical Subject Headings], Clinical Immunology, Polimorfismo de Nucleótido Simple, Antiinflamatorios no esteroideos, Phenomena and Processes::Genetic Phenomena::Gene Frequency [Medical Subject Headings], business, Population Genetics
Abstract

Journal Article; Research Support, Non-U.S. Gov't; Non-steroidal anti-inflammatory drugs (NSAIDs) are the drugs most frequently involved in hypersensitivity drug reactions. Histamine is released in the allergic response to NSAIDs and is responsible for some of the clinical symptoms. The aim of this study is to analyze clinical association of functional polymorphisms in the genes coding for enzymes involved in histamine homeostasis with hypersensitivity response to NSAIDs. We studied a cohort of 442 unrelated Caucasian patients with hypersensitivity to NSAIDs. Patients who experienced three or more episodes with two or more different NSAIDs were included. If this requirement was not met diagnosis was established by challenge. A total of 414 healthy unrelated controls ethnically matched with patients and from the same geographic area were recruited. Analyses of the SNPs rs17740607, rs2073440, rs1801105, rs2052129, rs10156191, rs1049742 and rs1049793 in the HDC, HNMT and DAO genes were carried out by means of TaqMan assays. The detrimental DAO 16 Met allele (rs10156191), which causes decreased metabolic capacity, is overrepresented among patients with crossed-hypersensitivity to NSAIDs with an OR = 1.7 (95% CI = 1.3-2.1; Pc = 0.0003) with a gene-dose effect (P = 0.0001). The association was replicated in two populations from different geographic areas (Pc = 0.008 and Pc = 0.004, respectively). CONCLUSIONS AND IMPLICATIONS: The DAO polymorphism rs10156191 which causes impaired metabolism of circulating histamine is associated with the clinical response in crossed-hypersensitivity to NSAIDs and could be used as a biomarker of response. Yes

Published
2012

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