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Article: Association of a functional IRF7 variant with systemic lupus erythematosus

TitleAssociation of a functional IRF7 variant with systemic lupus erythematosus
Authors
Issue Date2011
PublisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www.interscience.wiley.com/jpages/0004-3591/
Citation
Arthritis And Rheumatism, 2011, v. 63 n. 3, p. 749-754 How to Cite?
AbstractObjective. A previous genome-wide association study conducted in a population of European ancestry identified rs4963128, a KIAA1542 single-nucleotide polymorphism (SNP) 23 kb telomeric to IRF7 (the gene for interferon regulatory factor 7 [IRF-7]), to be strongly associated with systemic lupus erythematosus (SLE). This study was undertaken to investigate whether genetic polymorphism within IRF7 is a risk factor for the development of SLE. Methods. We genotyped one KIAA1542 SNP (rs4963128) and oneIRF7 SNP (rs1131665 [Q412R]) in an Asian population (1,302 cases, 1,479 controls), to assess their association with SLE. Subsequently, rs1131665 was further genotyped in independent panels of Chinese subjects (528 cases, 527 controls), European American subjects (446 cases, 461 controls), and African American subjects (159 cases, 115 controls) by TaqMan genotyping assay, to seek confirmation of association in various ethnic groups. A luciferase reporter assay was used to assess the effect of Q412R polymorphism on the activation of IRF-7. Results. Consistent association of rs1131665 (Q412R) with SLE was identified in Asian, European American, and African American populations (total 2,435 cases and 2,582 controls) (P meta = 6.18 x 10 -6, odds ratio 1.42 [95% confidence interval 1.22-1.65]). Expression of the IRF7 412Q risk allele resulted in a 2-fold increase in interferon-stimulated response element transcriptional activity compared with expression of IRF7 412R (P = 0.0003), suggesting that IRF7 412Q confers elevated IRF-7 activity and may therefore affect a downstream interferon pathway. Conclusion. These findings show that the major allele of a nonsynonymous SNP, rs1131665 (412Q) in IRF7, confers elevated activation of IRF-7 and predisposes to the development of SLE in multiple ethnic groups. This result provides direct genetic evidence that IRF7 may be a risk gene for human SLE. © 2011, American College of Rheumatology.
Persistent Identifierhttp://hdl.handle.net/10722/163369
ISSN
2015 Impact Factor: 8.955
2015 SCImago Journal Rankings: 3.206
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorFu, Qen_US
dc.contributor.authorZhao, Jen_US
dc.contributor.authorQian, Xen_US
dc.contributor.authorWong, JLHen_US
dc.contributor.authorKaufman, KMen_US
dc.contributor.authorYu, CYen_US
dc.contributor.authorHowe, HSen_US
dc.contributor.authorMok, MYen_US
dc.contributor.authorHarley, JBen_US
dc.contributor.authorGuthridge, JMen_US
dc.contributor.authorSong, YWen_US
dc.contributor.authorCho, SKen_US
dc.contributor.authorBae, SCen_US
dc.contributor.authorGrossman, JMen_US
dc.contributor.authorHahn, BHen_US
dc.contributor.authorArnett, FCen_US
dc.contributor.authorShen, Nen_US
dc.contributor.authorTsao, BPen_US
dc.date.accessioned2012-09-05T05:30:38Z-
dc.date.available2012-09-05T05:30:38Z-
dc.date.issued2011en_US
dc.identifier.citationArthritis And Rheumatism, 2011, v. 63 n. 3, p. 749-754en_US
dc.identifier.issn0004-3591en_US
dc.identifier.urihttp://hdl.handle.net/10722/163369-
dc.description.abstractObjective. A previous genome-wide association study conducted in a population of European ancestry identified rs4963128, a KIAA1542 single-nucleotide polymorphism (SNP) 23 kb telomeric to IRF7 (the gene for interferon regulatory factor 7 [IRF-7]), to be strongly associated with systemic lupus erythematosus (SLE). This study was undertaken to investigate whether genetic polymorphism within IRF7 is a risk factor for the development of SLE. Methods. We genotyped one KIAA1542 SNP (rs4963128) and oneIRF7 SNP (rs1131665 [Q412R]) in an Asian population (1,302 cases, 1,479 controls), to assess their association with SLE. Subsequently, rs1131665 was further genotyped in independent panels of Chinese subjects (528 cases, 527 controls), European American subjects (446 cases, 461 controls), and African American subjects (159 cases, 115 controls) by TaqMan genotyping assay, to seek confirmation of association in various ethnic groups. A luciferase reporter assay was used to assess the effect of Q412R polymorphism on the activation of IRF-7. Results. Consistent association of rs1131665 (Q412R) with SLE was identified in Asian, European American, and African American populations (total 2,435 cases and 2,582 controls) (P meta = 6.18 x 10 -6, odds ratio 1.42 [95% confidence interval 1.22-1.65]). Expression of the IRF7 412Q risk allele resulted in a 2-fold increase in interferon-stimulated response element transcriptional activity compared with expression of IRF7 412R (P = 0.0003), suggesting that IRF7 412Q confers elevated IRF-7 activity and may therefore affect a downstream interferon pathway. Conclusion. These findings show that the major allele of a nonsynonymous SNP, rs1131665 (412Q) in IRF7, confers elevated activation of IRF-7 and predisposes to the development of SLE in multiple ethnic groups. This result provides direct genetic evidence that IRF7 may be a risk gene for human SLE. © 2011, American College of Rheumatology.en_US
dc.languageengen_US
dc.publisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www.interscience.wiley.com/jpages/0004-3591/en_US
dc.relation.ispartofArthritis and Rheumatismen_US
dc.titleAssociation of a functional IRF7 variant with systemic lupus erythematosusen_US
dc.typeArticleen_US
dc.identifier.emailMok, MY:temy@hkucc.hku.hken_US
dc.identifier.authorityMok, MY=rp00490en_US
dc.description.naturelink_to_OA_fulltexten_US
dc.identifier.doi10.1002/art.30193en_US
dc.identifier.pmid21360504-
dc.identifier.scopuseid_2-s2.0-79953707345en_US
dc.identifier.hkuros217291-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-79953707345&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume63en_US
dc.identifier.issue3en_US
dc.identifier.spage749en_US
dc.identifier.epage754en_US
dc.identifier.isiWOS:000288095400027-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridFu, Q=24067143600en_US
dc.identifier.scopusauthoridZhao, J=36572944300en_US
dc.identifier.scopusauthoridQian, X=36572441800en_US
dc.identifier.scopusauthoridWong, JLH=37110384700en_US
dc.identifier.scopusauthoridKaufman, KM=7102773191en_US
dc.identifier.scopusauthoridYu, CY=7404977029en_US
dc.identifier.scopusauthoridHowe, HS=7103343933en_US
dc.identifier.scopusauthoridMok, MY=7006024184en_US
dc.identifier.scopusauthoridHarley, JB=7201902945en_US
dc.identifier.scopusauthoridGuthridge, JM=6602184825en_US
dc.identifier.scopusauthoridSong, YW=35075039400en_US
dc.identifier.scopusauthoridCho, SK=35185890800en_US
dc.identifier.scopusauthoridBae, SC=35309443700en_US
dc.identifier.scopusauthoridGrossman, JM=7202411114en_US
dc.identifier.scopusauthoridHahn, BH=7201798489en_US
dc.identifier.scopusauthoridArnett, FC=7004819793en_US
dc.identifier.scopusauthoridShen, N=7102785475en_US
dc.identifier.scopusauthoridTsao, BP=7005956550en_US

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