128 296

Cited 38 times in

Effect of single nucleotide polymorphisms within the interleukin-4 promoter on aspirin intolerance in asthmatics and interleukin-4 promoter activity.

Authors
Kim, BS; Park, SM; Uhm, TG; Kang, JH; Park, JS; Jang, AS; Uh, ST; Kim, MK; Choi, IS; Cho, SH; Hong, CS; Lee, YW; Lee, JY; Choi, BW; Park, HS; Park, BL; Shin, HD; Chung, IY; Park, CS
Citation
Pharmacogenetics and genomics, 20(12):748-758, 2010
Journal Title
Pharmacogenetics and genomics
ISSN
1744-68721744-6880
Abstract
OBJECTIVE: Aspirin affects interleukin-4 (IL-4) synthesis; however, the genetic role of IL-4 has not been evaluated in asthmatics with aspirin hypersensitivity. The objective of the study was to examine the influence of single nucleotide polymorphisms (SNPs) in IL-4 gene on aspirin hypersensitivity in asthmatics at the genetic and molecular levels. METHODS: Aspirin-intolerant (AIA, n=103) and aspirin-tolerant asthmatics (n=270) were genotyped and functional promoter assays were performed. RESULTS: Of 15 SNPs tested, seven (-589T>C (rs2243250) in promoter, -33T>C (rs2070874) in the 5'-untranslated region, +4047A>G (rs2243266), +4144C>G (rs2243267), +4221C>A (rs2243268), +4367G>A (rs2243270), and +5090A>G (rs2243274) in introns) were significantly associated with AIA risk. The frequency of the rare allele (C) of -589T>C was higher in the AIA group than in the aspirin-tolerant asthmatic group (P=0.016), and a gene dose-dependent decline in forced expiratory volume in 1 s was noted after an aspirin challenge (P=0.0009). Aspirin unregulated IL-4 mRNA production in Jurkat T and K562 leukemia cells. A reporter plasmid assay revealed that aspirin augmented IL-4 promoter transactivation with the -589T>C C and -33T>C C alleles, compared with that bearing the -589T>C T and -33T>C T alleles. Further, electrophoretic mobility shift assay showed the formation of nuclear complexes with -33T>C and -589T>C allele-containing probes; this was augmented by aspirin. The complexes formed with the -33T>C and -589T>C probes were shifted by treatment with anti-CCAAT-enhancer-binding proteins β and anti-nuclear factor of activated T-cells antibodies, respectively, indicating the inclusion of these transcription factors. CONCLUSION: Aspirin may regulate IL4 expression in an allele-specific manner by altering the availability of transcription factors to the key regulatory elements in the IL4 promoter, leading to aspirin hypersensitivity.
DOI
10.1097/FPC.0b013e3283402155
PMID
20921925
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Allergy
AJOU Authors
박해심
Full Text Link
Files in This Item:
Full-Text Not Available.txtDownload
Export
RIS (EndNote)
XLS (Excel)
XML

qrcode

해당 아이템을 이메일로 공유하기 원하시면 인증을 거치시기 바랍니다.

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse