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Article: TRAC variants associate with IgA nephropathy

TitleTRAC variants associate with IgA nephropathy
Authors
Issue Date2009
PublisherAmerican Society of Nephrology. The Journal's web site is located at http://www.jasn.org
Citation
Journal Of The American Society Of Nephrology, 2009, v. 20 n. 6, p. 1359-1367 How to Cite?
AbstractThe T cell receptor alpha constant gene (TRAC) encodes the constant region of the α chain for the T cell receptor, and the association of its gene variants with IgA nephropathy remains controversial. The authors resequenced the gene in 100 patients with IgA nephropathy and 100 controls, tested its linkage disequilibrium pattern, constructed haplotypes, and performed association and functional studies. First, the association between TRAC variants and IgA nephropathy was tested in 704 patients and 704 controls. Next, these 704 patients were divided into two independent datasets - 310 with family member(s) and 394 single patients - to test the association separately. Results showed that the gene is located in a recombination hot spot, with nine linkage disequilibrium blocks within a 6.9-kb region. There is a hypervariable region with six single-nucleotide polymorphisms (SNPs) in an 85-bp stretch in intron 1. We identified multiple SNPs and two haplotypes that associate with IgA nephropathy (P = 0.0000013-0.0096 by logistic regression for SNPs; P = 0.0003 and P = 0.0398 for haplotype associations). The family-based study replicated both haplotype findings, and the 394 single-patient case-control study replicated the association with haplotype 1 (P = 0.0033). The overtransmitted/observed haplotypes demonstrated reduced transcription activity compared with the undertransmitted/observed haplotypes. In conclusion, this study suggests an association between TRAC variants and susceptibility to IgA nephropathy. Copyright © 2009 by the American Society of Nephrology.
Persistent Identifierhttp://hdl.handle.net/10722/59371
ISSN
2015 Impact Factor: 8.491
2015 SCImago Journal Rankings: 4.699
PubMed Central ID
ISI Accession Number ID
Funding AgencyGrant Number
National Natural Science Foundation of China30570869
30771013
China Medical Board of New York05827
Guangdong Provincial Natural Science Foundation07001511
Funding Information:

The project was supported by the second phase of the State 985 Project of China, The National Natural Science Foundation of China (30570869 and 30771013), China Medical Board of New York (05827), and the Guangdong Provincial Natural Science Foundation (07001511). We thank Professor P. C. Sham, Department of Psychiatry, University of Hong Kong, for his advice. We also thank Dr. Yong Du for recruiting patients and families.

References

 

DC FieldValueLanguage
dc.contributor.authorLi, Ren_HK
dc.contributor.authorXue, Cen_HK
dc.contributor.authorLi, Cen_HK
dc.contributor.authorLou, Ten_HK
dc.contributor.authorTao, Yen_HK
dc.contributor.authorLi, Yen_HK
dc.contributor.authorHuang, Wen_HK
dc.contributor.authorZhang, Jen_HK
dc.contributor.authorLeung, JCKen_HK
dc.contributor.authorLam, MFen_HK
dc.contributor.authorVyse, TJen_HK
dc.contributor.authorLai, KNen_HK
dc.contributor.authorWu, Cen_HK
dc.contributor.authorWang, Yen_HK
dc.date.accessioned2010-05-31T03:48:38Z-
dc.date.available2010-05-31T03:48:38Z-
dc.date.issued2009en_HK
dc.identifier.citationJournal Of The American Society Of Nephrology, 2009, v. 20 n. 6, p. 1359-1367en_HK
dc.identifier.issn1046-6673en_HK
dc.identifier.urihttp://hdl.handle.net/10722/59371-
dc.description.abstractThe T cell receptor alpha constant gene (TRAC) encodes the constant region of the α chain for the T cell receptor, and the association of its gene variants with IgA nephropathy remains controversial. The authors resequenced the gene in 100 patients with IgA nephropathy and 100 controls, tested its linkage disequilibrium pattern, constructed haplotypes, and performed association and functional studies. First, the association between TRAC variants and IgA nephropathy was tested in 704 patients and 704 controls. Next, these 704 patients were divided into two independent datasets - 310 with family member(s) and 394 single patients - to test the association separately. Results showed that the gene is located in a recombination hot spot, with nine linkage disequilibrium blocks within a 6.9-kb region. There is a hypervariable region with six single-nucleotide polymorphisms (SNPs) in an 85-bp stretch in intron 1. We identified multiple SNPs and two haplotypes that associate with IgA nephropathy (P = 0.0000013-0.0096 by logistic regression for SNPs; P = 0.0003 and P = 0.0398 for haplotype associations). The family-based study replicated both haplotype findings, and the 394 single-patient case-control study replicated the association with haplotype 1 (P = 0.0033). The overtransmitted/observed haplotypes demonstrated reduced transcription activity compared with the undertransmitted/observed haplotypes. In conclusion, this study suggests an association between TRAC variants and susceptibility to IgA nephropathy. Copyright © 2009 by the American Society of Nephrology.en_HK
dc.languageengen_HK
dc.publisherAmerican Society of Nephrology. The Journal's web site is located at http://www.jasn.orgen_HK
dc.relation.ispartofJournal of the American Society of Nephrologyen_HK
dc.subject.meshBase Sequenceen_HK
dc.subject.meshCase-Control Studiesen_HK
dc.subject.meshGenes, T-Cell Receptor alphaen_HK
dc.subject.meshGenetic Predisposition to Diseaseen_HK
dc.subject.meshGlomerulonephritis, IGA - geneticsen_HK
dc.subject.meshHaplotypesen_HK
dc.subject.meshHumansen_HK
dc.subject.meshLinkage Disequilibriumen_HK
dc.subject.meshMolecular Sequence Dataen_HK
dc.subject.meshPolymorphism, Single Nucleotideen_HK
dc.subject.meshRNA, Messenger - metabolismen_HK
dc.subject.meshTranscription, Geneticen_HK
dc.titleTRAC variants associate with IgA nephropathyen_HK
dc.typeArticleen_HK
dc.identifier.emailLeung, JCK: jckleung@hku.hken_HK
dc.identifier.emailLai, KN: knlai@hku.hken_HK
dc.identifier.authorityLeung, JCK=rp00448en_HK
dc.identifier.authorityLai, KN=rp00324en_HK
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1681/ASN.2008080842en_HK
dc.identifier.pmid19470682-
dc.identifier.pmcidPMC2689895-
dc.identifier.scopuseid_2-s2.0-67449102468en_HK
dc.identifier.hkuros161398en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-67449102468&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume20en_HK
dc.identifier.issue6en_HK
dc.identifier.spage1359en_HK
dc.identifier.epage1367en_HK
dc.identifier.isiWOS:000266617200029-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridLi, R=55491291300en_HK
dc.identifier.scopusauthoridXue, C=12767328700en_HK
dc.identifier.scopusauthoridLi, C=26663041900en_HK
dc.identifier.scopusauthoridLou, T=7004047319en_HK
dc.identifier.scopusauthoridTao, Y=36121574400en_HK
dc.identifier.scopusauthoridLi, Y=8930727500en_HK
dc.identifier.scopusauthoridHuang, W=10041590500en_HK
dc.identifier.scopusauthoridZhang, J=7601342172en_HK
dc.identifier.scopusauthoridLeung, JCK=7202180349en_HK
dc.identifier.scopusauthoridLam, MF=35300050600en_HK
dc.identifier.scopusauthoridVyse, TJ=7003955999en_HK
dc.identifier.scopusauthoridLai, KN=7402135706en_HK
dc.identifier.scopusauthoridWu, C=7501660961en_HK
dc.identifier.scopusauthoridWang, Y=13310049900en_HK
dc.identifier.citeulike5937407-

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