Variants of CEP68 gene are associated with acute urticaria/angioedema induced by multiple non-steroidal anti-inflammatory drugs.

Szczegóły
Abstrakt

Tytuł:: Variants of CEP68 gene are associated with acute urticaria/angioedema induced by multiple non-steroidal anti-inflammatory drugs.
Autorzy:: Cornejo-García JA; Research Laboratory, IBIMA-Málaga University General Hospital, Málaga, Spain.
Flores C; Centro de Investigación Biomédica en Red (CIBER) de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain; Research Unit, Hospital Universitario N.S. de Candelaria, Tenerife, Spain; Applied Genomics Group (G2A), Genetics Laboratory, Instituto Universitario de Enfermedades Tropicales y Salud Pública de Canarias, Universidad de La Laguna, Tenerife, Spain.
Plaza-Serón MC; Research Laboratory, IBIMA-Málaga University General Hospital, Málaga, Spain.
Acosta-Herrera M; Centro de Investigación Biomédica en Red (CIBER) de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain; Research Unit, Hospital Universitario N.S. de Candelaria, Tenerife, Spain; Research Unit, Hospital Universitario Dr. Negrín, Las Palmas de Gran Canaria, Spain.
Blanca-López N; Allergy Service, Infanta Leonor Hospital, Madrid, Spain.
Doña I; Unidad de Gestión Clinica (UGC) Allergy-Instituto de Investigación Biomédica (IBIMA), Málaga University General Hospital, Málaga, Spain.
Torres MJ; Unidad de Gestión Clinica (UGC) Allergy-Instituto de Investigación Biomédica (IBIMA), Málaga University General Hospital, Málaga, Spain.
Mayorga C; Research Laboratory, IBIMA-Málaga University General Hospital, Málaga, Spain; Unidad de Gestión Clinica (UGC) Allergy-Instituto de Investigación Biomédica (IBIMA), Málaga University General Hospital, Málaga, Spain.
Guéant-Rodríguez RM; Institut National de la Santé et de la Recherche Médicale (INSERM) U-954, Nutrition-Génétique et exposition aux risques environmentaux, Faculty of Medicine, University of Nancy, Vandoeuvre-les-Nancy, France; University Hospital Center (CHU) of Nancy, Vandoeuvre-les-Nancy, France.
Ayuso P; Research Laboratory, IBIMA-Málaga University General Hospital, Málaga, Spain.
Fernández J; Allergy Service, Alicante Hospital, Alicante, Spain.
Laguna JJ; Allergy Service, Cruz Roja Central Hospital, Madrid, Spain.
Agúndez JA; Pharmacology Department, University of Extremadura, Cáceres, Spain.
García-Martín E; Biochemistry, Molecular Biology and Genetics Department, University of Extremadura, Cáceres, Spain.
Guéant JL; Institut National de la Santé et de la Recherche Médicale (INSERM) U-954, Nutrition-Génétique et exposition aux risques environmentaux, Faculty of Medicine, University of Nancy, Vandoeuvre-les-Nancy, France; University Hospital Center (CHU) of Nancy, Vandoeuvre-les-Nancy, France.
Canto G; Unidad de Gestión Clinica (UGC) Allergy-Instituto de Investigación Biomédica (IBIMA), Málaga University General Hospital, Málaga, Spain.
Blanca M; Research Unit, Hospital Universitario Dr. Negrín, Las Palmas de Gran Canaria, Spain.
Źródło:: PloS one [PLoS One] 2014 Mar 11; Vol. 9 (3), pp. e90966. Date of Electronic Publication: 2014 Mar 11 (Print Publication: 2014).
Typ publikacji:: Journal Article; Research Support, Non-U.S. Gov't
Język:: English
Imprint Name(s):: Original Publication: San Francisco, CA : Public Library of Science
MeSH Terms:: Genetic Variation*
Angioedema/*chemically induced
Angioedema/*genetics
Anti-Inflammatory Agents, Non-Steroidal/*adverse effects
Microtubule-Associated Proteins/*genetics
Adult ; Alleles ; Case-Control Studies ; Genetic Predisposition to Disease ; Humans ; Middle Aged ; Odds Ratio ; Polymorphism, Single Nucleotide
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Substance Nomenclature:: 0 (Anti-Inflammatory Agents, Non-Steroidal)
0 (CEP68 protein, human)
0 (Microtubule-Associated Proteins)
Entry Date(s):: Date Created: 20140313 Date Completed: 20150529 Latest Revision: 20211021
Update Code:: 20240104
PubMed Central ID:: PMC3949706
DOI:: 10.1371/journal.pone.0090966
PMID:: 24618698
: Czasopismo naukowe

Pełny tekst

Non-steroidal anti-inflammatory drugs (NSAIDs) are the most consumed drugs worldwide because of their efficacy and utility in the treatment of pain and inflammatory diseases. However, they are also responsible for an important number of adverse effects including hypersensitivity reactions. The most important group of these reactions is triggered by non-immunological, pharmacological mechanisms catalogued under the denomination of cross-intolerance (CRI), with acute urticaria/angioedema induced by multiple NSAIDs (MNSAID-UA) the most frequently associated clinical entity. A recent genome-wide association study identified the gene encoding the centrosomal protein of 68 KDa (CEP68) as the major locus associated with aspirin intolerance susceptibility in asthmatics. In this study, we aimed to assess the role of this locus in susceptibility to CRI to NSAIDs by examining 53 common gene variants in a total of 635 patients that were classified as MNSAID-UA (n = 399), airway exacerbations (n = 110) or blended pattern (n = 126), and 425 controls. We found in the MNSAID-UA group a number of variants (17) associated (lowest p-value = 1.13 × 10(-6)), including the non-synonymous Gly74Ser variant (rs7572857) previously associated with aspirin intolerance susceptibility in asthmatics. Although not being significant in the context of multiple testing, eight of these variants were also associated with exacerbated respiratory disease or blended reactions. Our results suggest that CEP68 gene variants may play an important role in MNSAID-UA susceptibility and, despite the different regulatory mechanisms involved depending on the specific affected organ, in the development of hypersensitivity reactions to NSAIDs.

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