Association between polymorphisms in prostanoid receptor genes and aspirin-intolerant asthma

Kim, Sang Heon; Kim, Yoon Keun; Park, Heung-Woo; Jee, Young Koo; Kim, Sang Hoon; Bahn, Jae Hoon; Chang, Yoon-Seok; Kim, Seung Hyun; Ye, Young-Min; Shin, Eak Kyun; Lee, Jong Eun; Park, Hae‐Sim; Min, Kyung Up

doi:10.1097/01.fpc.0000239977.61841.fe

Cited by 67 publications

(70 citation statements)

References 39 publications

(46 reference statements)

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“…7 Moreover, it was reported that the frequencies of GG homozygotes or heterozygotes of À1254A4G were significantly higher in AERD PTGER4 in aspirin-intolerant chronic urticaria NS Palikhe et al patients than in ATA patients or NCs. 16 This result indicates that the importance of genetic variations in PTGER4 À1254A4G to ones predisposition to AICU is similar with AERD. Mast cells are the key cell model for urticaria and release histamine and other chemical mediators, which produce urticarial symptoms, 20 and mast cell activation has been reported in ASA-intolerant urticaria patients.…”

Section: Discussionmentioning

confidence: 86%

“…We previously identified four polymorphisms of À1598 T4C (rs45437592), À1529 T4C (rs413301), À1307C4T (rs10039983) and À1254A4G (rs45613037) in the promoter region, and found significant association of À1254A4G with AERD. 16 Therefore, in this study, we chose À1254A4G SNP for genotyping with AICU, ATCU and NC using a primer extension method and the SNAPshot ddNTP primer extension kit. (Applied Biosystems, Foster City, CA, USA).…”

Section: Dna Extraction Snp Identification and Genotypingmentioning

confidence: 99%

“…3 Most candidate gene approaches have focused on leukotrienerelated pathways, whereas there have been no studies evaluating the effects of polymorphisms in PGE2 receptor genes on the development of AICU. Although PTGER4 À1254A4G promoter polymorphism was previously studied in the case of AERD, 16 no association study was noted in the case of AICU and functional study has not reported till now. Therefore, to replicate the effects of this promoter polymorphism in the other major phenotype of ASA hypersensitivity such as AICU, we performed genetic association study and to confirm the functional significance of promoter single-nucleotide polymorphism (SNP), we performed functional study in human mast cell 1 (HMC-1).…”

Section: Introductionmentioning

confidence: 97%

“…15 PTGER1, PTGER2, PTGER3 and PTGER4 polymorphism are the important genetic factors affecting the risk and severity of asthma as well as pathogenesis of AERD. [16][17][18] We recently reported that the other prostanoid receptor, thromboxane A2, (TBXA2R) À4684 T4C gene polymorphism is associated with aspirin-intolerant acute urticaria (AIAU). TBXA2R À4684 T allele may be associated with lower TBXA2R expression, which may contribute to the development of the AIAU phenotype.…”

Section: Introductionmentioning

confidence: 99%

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Genetic variability of prostaglandin E2 receptor subtype EP4 gene in aspirin-intolerant chronic urticaria

et al. 2012

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Prostaglandin E2 receptor subtype EP4 (PTGER4) is one of the four subtypes of receptors for prostaglandin E2 (PGE2). Overproduction of cysteinyl leukotriene in mast cells may be related with suppression of PGE2 in patients with aspirin hypersensitivity. Considering the association of PTGER4 in mast cells, urticaria-and aspirin-related disease, we hypothesized the genetic variability of PTGER4 may be associated with aspirin-intolerant chronic urticaria (AICU). The case-control study was performed in 141 with AICU, 153 with aspirin-tolerant chronic urticaria (ATCU) and 174 with normal controls (NCs). PTGER4 promoter single-nucleotide polymorphism was genotyped using a primer extension method with the SNAPshot ddNTP primer extension kit. The functional variability of PTGER4 promoter polymorphism was carried out by dual-luciferase system and electrophoretic mobility shift assay (EMSA) in human mast cells (HMC-1). Furthermore, the effect of aspirin was performed for PTGER4 mRNA expression using real-time PCR, and PGE2 production was checked in HMC-1 cells using ELISA. AICU patients carrying GG genotype at À1254 G4A showed significantly higher frequency compared with NC (P ¼ 0.032). Similarly, the minor allele frequency, G allele was significantly higher in AICU compared with NC (P ¼ 0.031). In vitro functional study demonstrated that the À1254 G allele had lower luciferase activity (Po0.001) in HMC-1 cells. EMSA finding showed that PTGER4 À1254 G produced a specific band. Significantly decreased PTGER4 expression (P ¼ 0.008) and PGE2 production by aspirin exposure was confirmed in in vitro HMC cell line model (P ¼ 0.001). The PTGER4 À1254 G allele demonstrated a higher frequency in AICU patients and lower promoter activity with decreased expression of PTGER4 and contributes to the development of AICU.

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Section: Discussionmentioning

confidence: 86%

Section: Dna Extraction Snp Identification and Genotypingmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

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Genetic variability of prostaglandin E2 receptor subtype EP4 gene in aspirin-intolerant chronic urticaria

et al. 2012

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“…Although a recent study suggested that the role of PGE2 in http://bmbreports.org the pathogenesis of asthma is independent of aspirin intolerance (23), others have shown that genetic variations in PGE2 receptors are strongly associated with AIA pathogenesis (24,25). Therefore, to replicate the effects of these genetic variations, we genotyped 120 polymorphisms of the PTGER gene family in a large case-control study of a Korean population and assessed their risk of AIA (n=1,162).…”

Section: Introductionmentioning

confidence: 99%

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

Park

Park²,

Park³

et al. 2010

BMB Reports

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Adaptive Set-Based Methods for Association Testing

Gauderman

Berhane

et al. 2015

Genet. Epidemiol.

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With a typical sample size of a few thousand subjects, a single genomewide association study (GWAS) using traditional one-SNP-at-a-time methods can only detect genetic variants conferring a sizable effect on disease risk. Set-based methods, which analyze sets of SNPs jointly, can detect variants with smaller effects acting within a gene, a pathway, or other biologically relevant sets. While self-contained set-based methods (those that test sets of variants without regard to variants not in the set) are generally more powerful than competitive set-based approaches (those that rely on comparison of variants in the set of interest with variants not in the set), there is no consensus as to which self-contained methods are best. In particular, several self-contained set tests have been proposed to directly or indirectly ‘adapt’ to the a priori unknown proportion and distribution of effects of the truly associated SNPs in the set, which is a major determinant of their power. A popular adaptive set-based test is the adaptive rank truncated product (ARTP), which seeks the set of SNPs that yields the best-combined evidence of association. We compared the standard ARTP, several ARTP variations we introduced, and other adaptive methods in a comprehensive simulation study to evaluate their performance. We used permutations to assess significance for all the methods and thus provide a level playing field for comparison. We found the standard ARTP test to have the highest power across our simulations followed closely by the global model of random effects (GMRE) and a LASSO based test.

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Association between polymorphisms in prostanoid receptor genes and aspirin-intolerant asthma

Cited by 67 publications

References 39 publications

Genetic variability of prostaglandin E2 receptor subtype EP4 gene in aspirin-intolerant chronic urticaria

Genetic variability of prostaglandin E2 receptor subtype EP4 gene in aspirin-intolerant chronic urticaria

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

Adaptive Set-Based Methods for Association Testing

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