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Association Analysis Between FILIP1 Polymorphisms and Aspirin Hypersensitivity in Korean Asthmatics.

ABSTRACT: PURPOSE:Aspirin exacerbated respiratory disease (AERD) results in a severe asthma attack after aspirin ingestion in asthmatics. The filamin A interacting protein 1 (FILIP1) may play a crucial role in AERD pathogenesis by mediating T cell activation and membrane rearrangement. We investigated the association of FILIP1 variations with AERD and the fall rate of forced expiratory volume in one second (FEV1). METHODS:A total of 34 common FILIP1 single nucleotide polymorphisms (SNPs) were genotyped in 592 Korean asthmatic subjects that included 163 AERD patients and 429 aspirin-tolerant asthma (ATA) controls. RESULTS:This study found that 5 SNPs (P=0.006-0.01) and 2 haplotypes (P=0.01-0.03) of FILIP1 showed nominal signals; however, corrections for the multiple testing revealed no significant associations with the development of AERD (P(corr)>0.05). In addition, association analysis of the genetic variants with the fall rate of FEV1, an important diagnostic marker of AERD, revealed no significant evidence (P(corr)>0.05). CONCLUSIONS:Although further replications and functional evaluations are needed, our preliminary findings suggest that genetic variants of FILIP1 might be not associated with the onset of AERD.

SUBMITTER: Kim JY

PROVIDER: S-EPMC3529227 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature

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Association Analysis Between FILIP1 Polymorphisms and Aspirin Hypersensitivity in Korean Asthmatics.

Kim Jason Yongha JY Kim Jeong-Hyun JH Park Byung-Lae BL Pasaje Charisse Flerida A CF Bae Joon Seol JS Park Jong Sook JS Jang An-Soo AS Uh Soo-Taek ST Kim Yong-Hoon YH Kim Mi-Kyeong MK Choi Inseon S IS Cho Sang Heon SH Choi Byoung Whui BW Park Choon-Sik CS Shin Hyoung Doo HD

Allergy, asthma & immunology research 20121025 1

<h4>Purpose</h4>Aspirin exacerbated respiratory disease (AERD) results in a severe asthma attack after aspirin ingestion in asthmatics. The filamin A interacting protein 1 (FILIP1) may play a crucial role in AERD pathogenesis by mediating T cell activation and membrane rearrangement. We investigated the association of FILIP1 variations with AERD and the fall rate of forced expiratory volume in one second (FEV1).<h4>Methods</h4>A total of 34 common FILIP1 single nucleotide polymorphisms (SNPs) we ...[more]

PMID: 23277876

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Project description:Background Aspirin exacerbated respiratory disease (AERD) is a syndrome characterized by chronic hyperplastic rhinosinusitis, nasal polyposis, asthma and aspirin sensitivity. The mechanisms by which produce these manifestations of intolerance are not fully defined, the current research involve alterations in the metabolism of arachidonic acid, cyclooxygenase 1 (COX-1) inhibition and its deviation from substrate to the lipoxygenase (LO) pathway, inducing increased synthesis of leukotrienes (LT). Biological plausibility of this fact has led to the search for polymorphisms in genes responsible for LT synthesis however others factors such as genetics polymorphisms in pro-inflammatory cytokines like, IL1B and IL8 could be associated. Methods 78 patients with AERD, 135 aspirin-tolerant asthma (ATA) and 134 healthy control subjects participated. All participants who underwent a simple spirometry, methacholine challenge and nasal challenge with Lysine-aspirin (L-ASA), both tests performed according to international guidelines. Peripheral blood was drawn by venipuncture, genomic DNA was obtained using the commercial BDtract DNA isolation kit. We selected 2 polymorphisms in 2 genes related to chronic inflammation rs16944 in IL1B, and rs4073 in IL8, Allelic discrimination of SNPs was performed by Real Time PCR (PCR-RT) on a 7300 Real Time PCR Systems. Statistical analysis was performed between groups of cases (AERD and ATA) versus control group with Epi-info v.6.04 by χ2 test to identify the difference between the allele and genotype frequencies of each polymorphism made, considering a significant P value <0.05, in addition to the calculation of odds ratios and confidence intervals of 95%. Results We find no association between IL1B (rs16944) to GG and GA genotypes in ATA patients versus control group neither AERD versus control group. Interestingly, the AA genotype showed increased frequency in the AERD patients versus the ATA patients (FG = 0.19 versus 0.07), this association remained significant (P = 0.018, OR 2.98, CI, 1.17-7.82). Conclusions This is the first observation that IL1B polymorphisms are involved in AERD, suggest that patients carrying out the IL1B-511 polymorphism (rs16944 AA genotype) may show enhanced susceptibility to develop AERD.

Dataset Information

Association Analysis Between FILIP1 Polymorphisms and Aspirin Hypersensitivity in Korean Asthmatics.

Publications

Association Analysis Between FILIP1 Polymorphisms and Aspirin Hypersensitivity in Korean Asthmatics.

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