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Effect of single nucleotide polymorphisms within the interleukin-4 promoter on aspirin intolerance in asthmatics and interleukin-4 promoter activity
DC Field | Value | Language |
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dc.contributor.author | Kim, Byung Soo | - |
dc.contributor.author | Park, Se-Min | - |
dc.contributor.author | Uhm, Tae Gi | - |
dc.contributor.author | Kang, Jin Hyun | - |
dc.contributor.author | Jang, An-Soo | - |
dc.contributor.author | Kim, Mi-Kyeong | - |
dc.contributor.author | Cho, Sang Heon | - |
dc.contributor.author | Lee, Yong Won | - |
dc.contributor.author | Choi, Byoung Whui | - |
dc.contributor.author | Park, Choon-Sik | - |
dc.contributor.author | Chung, Il Yup | - |
dc.contributor.author | Shin, Hyoung Doo | - |
dc.contributor.author | Park, Byung Lae | - |
dc.contributor.author | Park, Hae-Sim | - |
dc.contributor.author | Lee, Jae-Young | - |
dc.contributor.author | Hong, Cheon-Soo | - |
dc.contributor.author | Choi, Inseon S. | - |
dc.contributor.author | Uh, Soo-Taek | - |
dc.contributor.author | Park, Jong-Sook | - |
dc.date.accessioned | 2012-06-28T02:14:38Z | - |
dc.date.available | 2012-06-28T02:14:38Z | - |
dc.date.issued | 2010-12 | - |
dc.identifier.citation | PHARMACOGENETICS AND GENOMICS; Vol.20 12; 748-758 | ko_KR |
dc.identifier.issn | 1744-6872 | - |
dc.identifier.uri | https://hdl.handle.net/10371/77727 | - |
dc.description.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 aspirintolerant 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 50-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(corr) = 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 beta 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. Pharmacogenetics and Genomics 20:748-758 (C) 2010 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins. | ko_KR |
dc.description.sponsorship | This study was supported by the BK21, Korea
Research Foundation to B.S.K. and J.H.K., partially; and the Korea Health 21 R&D Project, Ministry of Health, Welfare and Family Affairs, Republic of Korea [A010249]. | ko_KR |
dc.language.iso | en | ko_KR |
dc.publisher | LIPPINCOTT WILLIAMS & WILKINS | ko_KR |
dc.subject | aspirin-intolerant asthmatics | ko_KR |
dc.subject | interleukin-4 | ko_KR |
dc.subject | promoter | ko_KR |
dc.subject | polymorphism | ko_KR |
dc.title | Effect of single nucleotide polymorphisms within the interleukin-4 promoter on aspirin intolerance in asthmatics and interleukin-4 promoter activity | ko_KR |
dc.type | Article | ko_KR |
dc.contributor.AlternativeAuthor | 김병수 | - |
dc.contributor.AlternativeAuthor | 박세민 | - |
dc.contributor.AlternativeAuthor | 엄태기 | - |
dc.contributor.AlternativeAuthor | 강진현 | - |
dc.contributor.AlternativeAuthor | 박종숙 | - |
dc.contributor.AlternativeAuthor | 장안수 | - |
dc.contributor.AlternativeAuthor | 어수택 | - |
dc.contributor.AlternativeAuthor | 김미경 | - |
dc.contributor.AlternativeAuthor | 최인선 | - |
dc.contributor.AlternativeAuthor | 조상헌 | - |
dc.contributor.AlternativeAuthor | 홍천수 | - |
dc.contributor.AlternativeAuthor | 이용원 | - |
dc.contributor.AlternativeAuthor | 이재영 | - |
dc.contributor.AlternativeAuthor | 최병휘 | - |
dc.contributor.AlternativeAuthor | 박해심 | - |
dc.contributor.AlternativeAuthor | 박병래 | - |
dc.contributor.AlternativeAuthor | 신형두 | - |
dc.contributor.AlternativeAuthor | 정일엽 | - |
dc.contributor.AlternativeAuthor | 박춘식 | - |
dc.identifier.doi | 10.1097/FPC.0b013e3283402155 | - |
dc.citation.journaltitle | PHARMACOGENETICS AND GENOMICS | - |
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dc.description.tc | 3 | - |
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