Genome-Wide and Follow-Up Studies Identify CEP68 Gene Variants Associated with Risk of Aspirin-Intolerant Asthma

Kim, Jeonghyun; Park, Byung-Lae; Cheong, Hyun Sub; Bae, Joon Seol; Park, Jong Suk; Jang, An Soo; Uh, Soo‐Taek; Choi, Ji‐Yeob; Kim, Yong‐Hoon; Kim, Mi-Kyeong; Choi, Inseon S.; Cho, Sang Heon; Choi, Byoung Whui; Park, Choon-Sik; Shin, Hyoung Doo

doi:10.1371/journal.pone.0013818

Cited by 70 publications

(69 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The authors found an intriguing association between the decline in FEV 1 and a nonsynonymous polymorphism (rs7572857, Gly74Ser) in centrosomal protein of 68 Kd (CEP68) [123], a gene involved in centrosomal cohesion and epidermal growth factor signaling [124,125]. Our group evaluated 53 common SNPs in this gene in a population of Spanish patients presenting NIUA, NERD, and blended reactions [126].…”

Section: Beyond the Candidate Gene Approachmentioning

confidence: 99%

Update on the Genetic Basis of Drug Hypersensitivity Reactions

Jurado‐Escobar¹,

Perkins²,

García‐Martín³

et al. 2017

J Investig Allergol Clin Immunol

View full text Add to dashboard Cite

Drug hypersensitivity reactions (DHRs) are unpredictable, complex responses to medicines in predisposed individuals. They represent a major health problem owing to the number of patients affected and the severity of the clinical conditions they can induce. In addition to environmental factors, the underlying mechanisms of DHRs are also influenced by genetic factors, although considerable gaps remain in our knowledge. Therefore, further study of the genetics of DHRs is necessary to shed light on their underlying mechanisms. In this manuscript, we provide an update on the genetic basis of the most frequent types of DHRs, including those mediated by immunological and nonimmunological mechanisms. For the first group, we will focus on immediate reactions to β-lactam antibiotics, which are associated mainly with the IgE pathway (IL13, IL4R, LGALS3, and NOD2) and antigen presentation (HLA-DRA), and nonimmediate reactions to allopurinol, anticonvulsants, antibiotics, and antiretrovirals, which are often associated with polymorphisms in the HLA system. For the second group, we will focus on nonsteroidal anti-inflammatory drugs, which are mostly associated with genetic variants in enzymes and receptors from the arachidonic acid pathway (eg, ALOX5, ALOX5AP, PTGDR, and CYSLTR1). The information provided here will be of interest for medical practitioners from a range of disciplines who come across these reactions in their clinical practice, as well as for allergologists. Key words: Drug hypersensitivity. Immunologically-mediated reactions. Cross-hypersensitivity. Single-nucleotide polymorphisms. Genomewide association study. ResumenLas reacciones de hipersensibilidad a fármacos (RHFs) son respuestas no predecibles que se producen en algunos sujetos y que representan un serio problema de salud pública debido al número de pacientes implicados y a su potencial gravedad. Además de factores ambientales, en estas reacciones también participan factores genéticos, cuya influencia está, en la mayoría de los casos, aún por dilucidar. En este manuscrito describiremos la información disponible sobre la base genética de los tipos más frecuentes de RHFs, tanto de las mediadas inmunológicamente como de aquellas en las que no se requiere reconocimiento antigénico. En el primer grupo nos ocuparemos de las reacciones inmediatas a antibióticos β-lactámicos, que han sido asociadas con variantes relacionadas con la IgE (IL13, IL4R, LGALS3 y NOD2) y la presentación antigénica (HLA-DRA), y de las reacciones no inmediatas a diferentes grupos de medicamentos (alopurinol, anticonvulsivos, antibióticos y antiretrovirales), relacionadas fundamentalmente con polimorfismos en el sistema HLA. En el segundo grupo nos centraremos en las reacciones inducidas por antiinflamatorios no esteroideos (AINE), que han sido asociadas básicamente con variantes en enzimas y receptores de la vía del ácido araquidónico (ALOX5, ALOX5AP, PTGDR y CYSLTR1, entre otros). Esta revisión puede ser de interés no sólo para alergólogos, sino para los profesionales de otras ...

show abstract

Section: Beyond the Candidate Gene Approachmentioning

confidence: 99%

Update on the Genetic Basis of Drug Hypersensitivity Reactions

Jurado‐Escobar¹,

Perkins²,

García‐Martín³

et al. 2017

J Investig Allergol Clin Immunol

View full text Add to dashboard Cite

show abstract

“…A recent genomewide association study highlighted the influence of the CEP68 (centrosomal protein of 68 KDa) gene on susceptibility to aspirin intolerance in asthmatics from Taiwan (62). A Spanish case-control study assessed the role of this locus in NAR to NSAIDs by examining 53 common gene variants in a total of 635 patients with NIUA (n = 399), NERD (n = 110) or blended pattern (n = 126), compared to 425 controls.…”

Section: Pathwaysmentioning

confidence: 99%

Genetic variants associated with drugs-induced immediate hypersensitivity reactions: a PRISMA-compliant systematic review

Oussalah

Mayorga

Blanca

et al. 2016

Allergy

View full text Add to dashboard Cite

Drug hypersensitivity includes allergic (AR) and nonallergic reactions (NARs) influenced by genetic predisposition. We performed a systematic review of genetic predictors of IgE-mediated AR and NAR with MEDLINE and PubMed search engine between January 1966 and December 2014. Among 3110 citations, the search selected 53 studies, 42 of which remained eligible. These eligible studies have evaluated genetic determinants of immediate reactions (IR) to beta-lactams (n = 19), NAR against aspirin (n = 12) and other nonsteroidal anti-inflammatory drugs (NSAIDs) (n = 8), and IR to biologics (n = 3). We reported two genomewide association studies and four case-control studies on candidate genes validated by replication. Genes involved in IR to beta-lactams belonged to HLA type 2 antigen processing, IgE production, atopy, and inflammation, including 4 genes validated by replications, HLA-DRA, ILR4, NOD2, and LGALS3. Genes involved in NAR to aspirin belonged to arachidonic acid pathway, membranespanning 4A gene family, histamine production pathway, and pro-inflammatory cytokines, while those involved in NAR to all NSAIDs belonged to arachidonic acid pathway and HLA antigen processing pathway. ALOX5 was a common predictor of studies on NAR to both aspirin and NSAIDs. Although these first conclusions could be drawn, this review highlights also the lack of reliable data and the need for replicating studies in contrasted populations, taking into account worldwide allele frequencies, gene-gene interactions, and contrasted situations of environmental exposure.Allergy 71 (2016) 443-462

show abstract

“…[ 94] greater than that seen for complex diseases. GWASs with sample sizes as low as 22 have produced highly significant findings [23].…”

Section: Cep68mentioning

confidence: 99%

State-of-the-Art Technologies to Interrogate Genetic/Genomic Components of Drug Response

Banerjee¹,

2013

Curr Genet Med Rep

View full text Add to dashboard Cite

Over the last decade, the study of genomes has rapidly advanced to the point that genomic research now serves as the basis for many medical decisions and public health initiatives. Genetic variation is likely to contribute substantially to the variation in drug response observed across human populations. Genomic tools such as sequence variation and, more specifically, personal genome sequencing incorporating genome-wide association studies and nextgeneration sequences enable the precise prediction and treatment of disease. At present, DNA-based risk assessment for common complex diseases, application of molecular signatures and dose selection of therapeutic drugs are the important issues in personalized medicine. In order to make personalized medicine effective, these genomic techniques must be standardized and integrated into health systems and clinical workflow for prediction of disease incidence, genetic and environmental information to optimize the medical care and outcomes for each patient. Technology continues to lead the field of personalized medicine since the interpretation of the human genome is progressing as the cost and duration of genomic sequencing continue to decrease sharply. This review aimed at understanding the technologies that reveal how the changes that occur within the genome can alter their functions and the genomic variations that constitute individual susceptibility to diseases and responses to therapy.

show abstract

Genome-Wide and Follow-Up Studies Identify CEP68 Gene Variants Associated with Risk of Aspirin-Intolerant Asthma

Cited by 70 publications

References 51 publications

Update on the Genetic Basis of Drug Hypersensitivity Reactions

Update on the Genetic Basis of Drug Hypersensitivity Reactions

Genetic variants associated with drugs-induced immediate hypersensitivity reactions: a PRISMA-compliant systematic review

State-of-the-Art Technologies to Interrogate Genetic/Genomic Components of Drug Response

Contact Info

Product

Resources

About