Association of PTGER gene family polymorphisms with aspirin intolerant asthma in Korean asthmatics

Park, Byung Lae; Park, Se Min; Park, Jong Suk; Uh, Soo Taek; Choi, Jae Sung; Kim, Yong Hoon; Kim, Mi Kyeong; Choi, Inseon S.; Choi, Byoung Whui; Cho, Sang Heon; Hong, Chein Soo; Lee, Yong Won; Lee, Jae Young; Park, Choon-Sik; Shin, Hyoung Doo

doi:10.5483/bmbrep.2010.43.6.445

Cited by 29 publications

(13 citation statements)

References 26 publications

(29 reference statements)

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“…Polymorphisms in its receptor PTGER2 were mainly found to be associated with aspirin-intolerant asthma, but in some studies also with asthma in general [46]. In our study the distribution of the SNPs in the PTGER2 gene did not differ between the asthmatic and control groups.…”

Section: Discussioncontrasting

confidence: 46%

Evaluation of a Partial Genome Screening of Two Asthma Susceptibility Regions Using Bayesian Network Based Bayesian Multilevel Analysis of Relevance

et al. 2012

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Genetic studies indicate high number of potential factors related to asthma. Based on earlier linkage analyses we selected the 11q13 and 14q22 asthma susceptibility regions, for which we designed a partial genome screening study using 145 SNPs in 1201 individuals (436 asthmatic children and 765 controls). The results were evaluated with traditional frequentist methods and we applied a new statistical method, called Bayesian network based Bayesian multilevel analysis of relevance (BN-BMLA). This method uses Bayesian network representation to provide detailed characterization of the relevance of factors, such as joint significance, the type of dependency, and multi-target aspects. We estimated posteriors for these relations within the Bayesian statistical framework, in order to estimate the posteriors whether a variable is directly relevant or its association is only mediated. With frequentist methods one SNP (rs3751464 in the FRMD6 gene) provided evidence for an association with asthma (OR = 1.43(1.2–1.8); p = 3×10 −4 ). The possible role of the FRMD6 gene in asthma was also confirmed in an animal model and human asthmatics. In the BN-BMLA analysis altogether 5 SNPs in 4 genes were found relevant in connection with asthma phenotype: PRPF19 on chromosome 11, and FRMD6 , PTGER2 and PTGDR on chromosome 14. In a subsequent step a partial dataset containing rhinitis and further clinical parameters was used, which allowed the analysis of relevance of SNPs for asthma and multiple targets. These analyses suggested that SNPs in the AHNAK and MS4A2 genes were indirectly associated with asthma. This paper indicates that BN-BMLA explores the relevant factors more comprehensively than traditional statistical methods and extends the scope of strong relevance based methods to include partial relevance, global characterization of relevance and multi-target relevance.

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Section: Discussioncontrasting

confidence: 46%

Evaluation of a Partial Genome Screening of Two Asthma Susceptibility Regions Using Bayesian Network Based Bayesian Multilevel Analysis of Relevance

et al. 2012

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“…The prostaglandin E2 receptor subtype 2 gene ( PTGER2 ) was associated with the risk of AERD by decreasing the level of transcription, resulting in a reduction of the “PGE2 braking” mechanism of inflammation and involvement in the molecular mechanism underlying AERD in the Japanese population [24]. A further report in the Korean population showed that prostaglandin E2 receptor subtype 3 ( PTGER3 ) may be an important genetic factor for aspirin intolerance in Korean asthmatics [25]. The human leukocyte antigen (HLA) allele DPB 1*0301 was identified as a strong marker for AERD, because patients with this allele showed typical characteristics of AERD including a decreased forced expiratory volume in 1 s (FEV 1 ) and increased prevalence of rhinosinusitis with nasal polyps [26], as previously noted in a Polish population [27].…”

Section: Key Results Regarding Genetic Mechanismsmentioning

confidence: 99%

Genetic Mechanisms in Aspirin-Exacerbated Respiratory Disease

et al. 2012

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Aspirin-exacerbated respiratory disease (AERD) refers to the development of bronchoconstriction in asthmatics following the exposure to aspirin or other nonsteroidal anti-inflammatory drugs. The key pathogenic mechanisms associated with AERD are the overproduction of cysteinyl leukotrienes (CysLTs) and increased CysLTR1 expression in the airway mucosa and decreased lipoxin and PGE2 synthesis. Genetic studies have suggested a role for variability of genes in disease susceptibility and the response to medication. Potential genetic biomarkers contributing to the AERD phenotype include HLA-DPB1, LTC4S, ALOX5, CYSLT, PGE2, TBXA2R, TBX21, MS4A2, IL10, ACE, IL13, KIF3A, SLC22A2, CEP68, PTGER, and CRTH2 and a four-locus SNP set composed of B2ADR, CCR3, CysLTR1, and FCER1B. Future areas of investigation need to focus on comprehensive approaches to identifying biomarkers for early diagnosis.

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“…1F). 30 In the case of PTGER4, the frequencies of GG homozygotes and heterozygotes of -1254A>G in the promoter region were significantly higher in AIA than in ATA patients (Table 2 and Fig. 1F).…”

Section: Candidate Gene Association Study Using Snps Of Arachidonate mentioning

confidence: 89%

Unraveling the Genetic Basis of Aspirin Hypersensitivity in Asthma Beyond Arachidonate Pathways

Park

et al. 2013

Allergy Asthma Immunol Res

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Although aspirin-exacerbated respiratory disease (AERD) has attracted a great deal of attention because of its association with severe asthma, it remains widely under-diagnosed in the asthmatic population. Oral aspirin challenge is the best method of diagnosing AERD, but this is a time-consuming procedure with serious complications in some cases. Thus, development of non-invasive methods for easy diagnosis is necessary to prevent unexpected complications of aspirin use in susceptible patients. For the past decade, many studies have attempted to elucidate the genetic variants responsible for risk of AERD. Several approaches have been applied in these genetic studies. To date, a limited number of biologically plausible candidate genes in the arachidonate and immune and inflammatory pathways have been studied. Recently, a genome-wide association study was performed. In this review, the results of these studies are summarized, and their limitations discussed. In addition to the genetic variants, changes in methylation patterns on CpG sites have recently been identified in a target tissue of aspirin hypersensitivity. Finally, perspectives on application of new genomic technologies are introduced; these will aid our understanding of the genetic pathogenesis of aspirin hypersensitivity in asthma.

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Association of PTGER gene family polymorphisms with aspirin intolerant asthma in Korean asthmatics

Cited by 29 publications

References 26 publications

Evaluation of a Partial Genome Screening of Two Asthma Susceptibility Regions Using Bayesian Network Based Bayesian Multilevel Analysis of Relevance

Evaluation of a Partial Genome Screening of Two Asthma Susceptibility Regions Using Bayesian Network Based Bayesian Multilevel Analysis of Relevance

Genetic Mechanisms in Aspirin-Exacerbated Respiratory Disease

Unraveling the Genetic Basis of Aspirin Hypersensitivity in Asthma Beyond Arachidonate Pathways

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