Effect of single nucleotide polymorphisms within the interleukin-4 promoter on aspirin intolerance in asthmatics and interleukin-4 promoter activity
OBJECTIVEAspirin 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...
Gespeichert in:
| Veröffentlicht in: | Pharmacogenetics and genomics 2010-12, Vol.20 (12), p.748-758 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 758 |
|---|---|
| container_issue | 12 |
| container_start_page | 748 |
| container_title | Pharmacogenetics and genomics |
| container_volume | 20 |
| creator | Kim, Byung Soo Park, Se-Min Uhm, Tae Gi Kang, Jin Hyun Park, Jong-Sook Jang, An-Soo Uh, Soo-Taek Kim, Mi-Kyeong Choi, Inseon S Cho, Sang Heon Hong, Cheon-Soo Lee, Yong Won Lee, Jae-Young Choi, Byoung Whui Park, Hae-Sim Park, Byung Lae Shin, Hyoung Doo Chung, Il Yup Park, Choon-Sik |
| description | OBJECTIVEAspirin 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.
METHODSAspirin-intolerant (AIA, n=103) and aspirin-tolerant asthmatics (n=270) were genotyped and functional promoter assays were performed.
RESULTSOf 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.
CONCLUSIONAspirin 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_str_mv | 10.1097/FPC.0b013e3283402155 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_847596707</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>847596707</sourcerecordid><originalsourceid>FETCH-LOGICAL-c3813-57c6fb1cdb9e1414e57a279a3a4f3303f6da2b7afe75effcd2a81f7cdd78e6413</originalsourceid><addsrcrecordid>eNp1kd-K1TAQxoso7rr6BiK5Ea-6Tv60aS_lsKvCgl7odUjTiY2bNjVJPZz38IHNYY9HELwIE4bfNzN8X1W9pHBNoZdvbz_vrmEAypGzjgtgtGkeVZdUClG3XQePz3_JLqpnKX0H4G0v2NPqgkHPaM-ay-rXjbVoMgmWJLd880iWzXgM2Y1I1uAPc4jr5NKcyN7lyS0kT0jckjF63O7dUguyxjCH0iBhITqtLhaqEMFj1Is50qWdp1lnZxLRy_g_vTbZ_XT58Lx6YrVP-OJUr6qvtzdfdh_qu0_vP-7e3dWGd5TXjTStHagZhx6poAIbqZnsNdfCcg7ctqNmg9QWZYPWmpHpjlppxlF22ArKr6o3D3PLBT82TFnNLhn0Xi8YtqQ6IZu-lSALKR5IE0NKEa1ao5t1PCgK6hiHKnGof-MoslenBdsw43gW_fG_AK9PgE5Ge3s0zKW_HG8Z0JLbef8--OJUuvfbHqOaUPs8KaCMcqC0PsKUAUBdHnD-G9H3p4g</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>847596707</pqid></control><display><type>article</type><title>Effect of single nucleotide polymorphisms within the interleukin-4 promoter on aspirin intolerance in asthmatics and interleukin-4 promoter activity</title><source>MEDLINE</source><source>Journals@Ovid Complete</source><creator>Kim, Byung Soo ; Park, Se-Min ; Uhm, Tae Gi ; Kang, Jin Hyun ; Park, Jong-Sook ; Jang, An-Soo ; Uh, Soo-Taek ; Kim, Mi-Kyeong ; Choi, Inseon S ; Cho, Sang Heon ; Hong, Cheon-Soo ; Lee, Yong Won ; Lee, Jae-Young ; Choi, Byoung Whui ; Park, Hae-Sim ; Park, Byung Lae ; Shin, Hyoung Doo ; Chung, Il Yup ; Park, Choon-Sik</creator><creatorcontrib>Kim, Byung Soo ; Park, Se-Min ; Uhm, Tae Gi ; Kang, Jin Hyun ; Park, Jong-Sook ; Jang, An-Soo ; Uh, Soo-Taek ; Kim, Mi-Kyeong ; Choi, Inseon S ; Cho, Sang Heon ; Hong, Cheon-Soo ; Lee, Yong Won ; Lee, Jae-Young ; Choi, Byoung Whui ; Park, Hae-Sim ; Park, Byung Lae ; Shin, Hyoung Doo ; Chung, Il Yup ; Park, Choon-Sik</creatorcontrib><description>OBJECTIVEAspirin 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.
METHODSAspirin-intolerant (AIA, n=103) and aspirin-tolerant asthmatics (n=270) were genotyped and functional promoter assays were performed.
RESULTSOf 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.
CONCLUSIONAspirin 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.</description><identifier>ISSN: 1744-6872</identifier><identifier>EISSN: 1744-6880</identifier><identifier>DOI: 10.1097/FPC.0b013e3283402155</identifier><identifier>PMID: 20921925</identifier><language>eng</language><publisher>Hagerstown, MD: Lippincott Williams & Wilkins, Inc</publisher><subject>Adolescent ; Adult ; Aged ; Aspirin - pharmacology ; Asthma - genetics ; Biological and medical sciences ; Cell Nucleus - drug effects ; Cell Nucleus - metabolism ; Chromosome Mapping ; Chronic obstructive pulmonary disease, asthma ; Drug Tolerance - genetics ; Female ; Gene Frequency - genetics ; General pharmacology ; Genetic Predisposition to Disease ; Heterozygote ; Humans ; Interleukin-4 - genetics ; Jurkat Cells ; K562 Cells ; Logistic Models ; Male ; Medical sciences ; Middle Aged ; Pharmacokinetics. Pharmacogenetics. Drug-receptor interactions ; Pharmacology. Drug treatments ; Pneumology ; Polymorphism, Single Nucleotide - genetics ; Promoter Regions, Genetic - genetics ; Protein Binding - drug effects ; Risk Factors ; Transcription Factors - metabolism ; Transcription, Genetic - drug effects ; Young Adult</subject><ispartof>Pharmacogenetics and genomics, 2010-12, Vol.20 (12), p.748-758</ispartof><rights>2010 Lippincott Williams & Wilkins, Inc.</rights><rights>2015 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3813-57c6fb1cdb9e1414e57a279a3a4f3303f6da2b7afe75effcd2a81f7cdd78e6413</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27903,27904</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=23620100$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20921925$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kim, Byung Soo</creatorcontrib><creatorcontrib>Park, Se-Min</creatorcontrib><creatorcontrib>Uhm, Tae Gi</creatorcontrib><creatorcontrib>Kang, Jin Hyun</creatorcontrib><creatorcontrib>Park, Jong-Sook</creatorcontrib><creatorcontrib>Jang, An-Soo</creatorcontrib><creatorcontrib>Uh, Soo-Taek</creatorcontrib><creatorcontrib>Kim, Mi-Kyeong</creatorcontrib><creatorcontrib>Choi, Inseon S</creatorcontrib><creatorcontrib>Cho, Sang Heon</creatorcontrib><creatorcontrib>Hong, Cheon-Soo</creatorcontrib><creatorcontrib>Lee, Yong Won</creatorcontrib><creatorcontrib>Lee, Jae-Young</creatorcontrib><creatorcontrib>Choi, Byoung Whui</creatorcontrib><creatorcontrib>Park, Hae-Sim</creatorcontrib><creatorcontrib>Park, Byung Lae</creatorcontrib><creatorcontrib>Shin, Hyoung Doo</creatorcontrib><creatorcontrib>Chung, Il Yup</creatorcontrib><creatorcontrib>Park, Choon-Sik</creatorcontrib><title>Effect of single nucleotide polymorphisms within the interleukin-4 promoter on aspirin intolerance in asthmatics and interleukin-4 promoter activity</title><title>Pharmacogenetics and genomics</title><addtitle>Pharmacogenet Genomics</addtitle><description>OBJECTIVEAspirin 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.
METHODSAspirin-intolerant (AIA, n=103) and aspirin-tolerant asthmatics (n=270) were genotyped and functional promoter assays were performed.
RESULTSOf 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.
CONCLUSIONAspirin 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.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Aspirin - pharmacology</subject><subject>Asthma - genetics</subject><subject>Biological and medical sciences</subject><subject>Cell Nucleus - drug effects</subject><subject>Cell Nucleus - metabolism</subject><subject>Chromosome Mapping</subject><subject>Chronic obstructive pulmonary disease, asthma</subject><subject>Drug Tolerance - genetics</subject><subject>Female</subject><subject>Gene Frequency - genetics</subject><subject>General pharmacology</subject><subject>Genetic Predisposition to Disease</subject><subject>Heterozygote</subject><subject>Humans</subject><subject>Interleukin-4 - genetics</subject><subject>Jurkat Cells</subject><subject>K562 Cells</subject><subject>Logistic Models</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Pharmacokinetics. Pharmacogenetics. Drug-receptor interactions</subject><subject>Pharmacology. Drug treatments</subject><subject>Pneumology</subject><subject>Polymorphism, Single Nucleotide - genetics</subject><subject>Promoter Regions, Genetic - genetics</subject><subject>Protein Binding - drug effects</subject><subject>Risk Factors</subject><subject>Transcription Factors - metabolism</subject><subject>Transcription, Genetic - drug effects</subject><subject>Young Adult</subject><issn>1744-6872</issn><issn>1744-6880</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kd-K1TAQxoso7rr6BiK5Ea-6Tv60aS_lsKvCgl7odUjTiY2bNjVJPZz38IHNYY9HELwIE4bfNzN8X1W9pHBNoZdvbz_vrmEAypGzjgtgtGkeVZdUClG3XQePz3_JLqpnKX0H4G0v2NPqgkHPaM-ay-rXjbVoMgmWJLd880iWzXgM2Y1I1uAPc4jr5NKcyN7lyS0kT0jckjF63O7dUguyxjCH0iBhITqtLhaqEMFj1Is50qWdp1lnZxLRy_g_vTbZ_XT58Lx6YrVP-OJUr6qvtzdfdh_qu0_vP-7e3dWGd5TXjTStHagZhx6poAIbqZnsNdfCcg7ctqNmg9QWZYPWmpHpjlppxlF22ArKr6o3D3PLBT82TFnNLhn0Xi8YtqQ6IZu-lSALKR5IE0NKEa1ao5t1PCgK6hiHKnGof-MoslenBdsw43gW_fG_AK9PgE5Ge3s0zKW_HG8Z0JLbef8--OJUuvfbHqOaUPs8KaCMcqC0PsKUAUBdHnD-G9H3p4g</recordid><startdate>201012</startdate><enddate>201012</enddate><creator>Kim, Byung Soo</creator><creator>Park, Se-Min</creator><creator>Uhm, Tae Gi</creator><creator>Kang, Jin Hyun</creator><creator>Park, Jong-Sook</creator><creator>Jang, An-Soo</creator><creator>Uh, Soo-Taek</creator><creator>Kim, Mi-Kyeong</creator><creator>Choi, Inseon S</creator><creator>Cho, Sang Heon</creator><creator>Hong, Cheon-Soo</creator><creator>Lee, Yong Won</creator><creator>Lee, Jae-Young</creator><creator>Choi, Byoung Whui</creator><creator>Park, Hae-Sim</creator><creator>Park, Byung Lae</creator><creator>Shin, Hyoung Doo</creator><creator>Chung, Il Yup</creator><creator>Park, Choon-Sik</creator><general>Lippincott Williams & Wilkins, Inc</general><general>Lippincott Williams & Wilkins</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>201012</creationdate><title>Effect of single nucleotide polymorphisms within the interleukin-4 promoter on aspirin intolerance in asthmatics and interleukin-4 promoter activity</title><author>Kim, Byung Soo ; Park, Se-Min ; Uhm, Tae Gi ; Kang, Jin Hyun ; Park, Jong-Sook ; Jang, An-Soo ; Uh, Soo-Taek ; Kim, Mi-Kyeong ; Choi, Inseon S ; Cho, Sang Heon ; Hong, Cheon-Soo ; Lee, Yong Won ; Lee, Jae-Young ; Choi, Byoung Whui ; Park, Hae-Sim ; Park, Byung Lae ; Shin, Hyoung Doo ; Chung, Il Yup ; Park, Choon-Sik</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3813-57c6fb1cdb9e1414e57a279a3a4f3303f6da2b7afe75effcd2a81f7cdd78e6413</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Aged</topic><topic>Aspirin - pharmacology</topic><topic>Asthma - genetics</topic><topic>Biological and medical sciences</topic><topic>Cell Nucleus - drug effects</topic><topic>Cell Nucleus - metabolism</topic><topic>Chromosome Mapping</topic><topic>Chronic obstructive pulmonary disease, asthma</topic><topic>Drug Tolerance - genetics</topic><topic>Female</topic><topic>Gene Frequency - genetics</topic><topic>General pharmacology</topic><topic>Genetic Predisposition to Disease</topic><topic>Heterozygote</topic><topic>Humans</topic><topic>Interleukin-4 - genetics</topic><topic>Jurkat Cells</topic><topic>K562 Cells</topic><topic>Logistic Models</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Pharmacokinetics. Pharmacogenetics. Drug-receptor interactions</topic><topic>Pharmacology. Drug treatments</topic><topic>Pneumology</topic><topic>Polymorphism, Single Nucleotide - genetics</topic><topic>Promoter Regions, Genetic - genetics</topic><topic>Protein Binding - drug effects</topic><topic>Risk Factors</topic><topic>Transcription Factors - metabolism</topic><topic>Transcription, Genetic - drug effects</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kim, Byung Soo</creatorcontrib><creatorcontrib>Park, Se-Min</creatorcontrib><creatorcontrib>Uhm, Tae Gi</creatorcontrib><creatorcontrib>Kang, Jin Hyun</creatorcontrib><creatorcontrib>Park, Jong-Sook</creatorcontrib><creatorcontrib>Jang, An-Soo</creatorcontrib><creatorcontrib>Uh, Soo-Taek</creatorcontrib><creatorcontrib>Kim, Mi-Kyeong</creatorcontrib><creatorcontrib>Choi, Inseon S</creatorcontrib><creatorcontrib>Cho, Sang Heon</creatorcontrib><creatorcontrib>Hong, Cheon-Soo</creatorcontrib><creatorcontrib>Lee, Yong Won</creatorcontrib><creatorcontrib>Lee, Jae-Young</creatorcontrib><creatorcontrib>Choi, Byoung Whui</creatorcontrib><creatorcontrib>Park, Hae-Sim</creatorcontrib><creatorcontrib>Park, Byung Lae</creatorcontrib><creatorcontrib>Shin, Hyoung Doo</creatorcontrib><creatorcontrib>Chung, Il Yup</creatorcontrib><creatorcontrib>Park, Choon-Sik</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Pharmacogenetics and genomics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kim, Byung Soo</au><au>Park, Se-Min</au><au>Uhm, Tae Gi</au><au>Kang, Jin Hyun</au><au>Park, Jong-Sook</au><au>Jang, An-Soo</au><au>Uh, Soo-Taek</au><au>Kim, Mi-Kyeong</au><au>Choi, Inseon S</au><au>Cho, Sang Heon</au><au>Hong, Cheon-Soo</au><au>Lee, Yong Won</au><au>Lee, Jae-Young</au><au>Choi, Byoung Whui</au><au>Park, Hae-Sim</au><au>Park, Byung Lae</au><au>Shin, Hyoung Doo</au><au>Chung, Il Yup</au><au>Park, Choon-Sik</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effect of single nucleotide polymorphisms within the interleukin-4 promoter on aspirin intolerance in asthmatics and interleukin-4 promoter activity</atitle><jtitle>Pharmacogenetics and genomics</jtitle><addtitle>Pharmacogenet Genomics</addtitle><date>2010-12</date><risdate>2010</risdate><volume>20</volume><issue>12</issue><spage>748</spage><epage>758</epage><pages>748-758</pages><issn>1744-6872</issn><eissn>1744-6880</eissn><abstract>OBJECTIVEAspirin 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.
METHODSAspirin-intolerant (AIA, n=103) and aspirin-tolerant asthmatics (n=270) were genotyped and functional promoter assays were performed.
RESULTSOf 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.
CONCLUSIONAspirin 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.</abstract><cop>Hagerstown, MD</cop><pub>Lippincott Williams & Wilkins, Inc</pub><pmid>20921925</pmid><doi>10.1097/FPC.0b013e3283402155</doi><tpages>11</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1744-6872 |
| ispartof | Pharmacogenetics and genomics, 2010-12, Vol.20 (12), p.748-758 |
| issn | 1744-6872 1744-6880 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_847596707 |
| source | MEDLINE; Journals@Ovid Complete |
| subjects | Adolescent Adult Aged Aspirin - pharmacology Asthma - genetics Biological and medical sciences Cell Nucleus - drug effects Cell Nucleus - metabolism Chromosome Mapping Chronic obstructive pulmonary disease, asthma Drug Tolerance - genetics Female Gene Frequency - genetics General pharmacology Genetic Predisposition to Disease Heterozygote Humans Interleukin-4 - genetics Jurkat Cells K562 Cells Logistic Models Male Medical sciences Middle Aged Pharmacokinetics. Pharmacogenetics. Drug-receptor interactions Pharmacology. Drug treatments Pneumology Polymorphism, Single Nucleotide - genetics Promoter Regions, Genetic - genetics Protein Binding - drug effects Risk Factors Transcription Factors - metabolism Transcription, Genetic - drug effects Young Adult |
| title | Effect of single nucleotide polymorphisms within the interleukin-4 promoter on aspirin intolerance in asthmatics and interleukin-4 promoter activity |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-26T07%3A05%3A36IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Effect%20of%20single%20nucleotide%20polymorphisms%20within%20the%20interleukin-4%20promoter%20on%20aspirin%20intolerance%20in%20asthmatics%20and%20interleukin-4%20promoter%20activity&rft.jtitle=Pharmacogenetics%20and%20genomics&rft.au=Kim,%20Byung%20Soo&rft.date=2010-12&rft.volume=20&rft.issue=12&rft.spage=748&rft.epage=758&rft.pages=748-758&rft.issn=1744-6872&rft.eissn=1744-6880&rft_id=info:doi/10.1097/FPC.0b013e3283402155&rft_dat=%3Cproquest_cross%3E847596707%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=847596707&rft_id=info:pmid/20921925&rfr_iscdi=true |