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Article: Association of -27T>C and its haplotype at the putative promoter for IgA-specific receptor gene with IgA nephropathy among the Chinese Han population

TitleAssociation of -27T>C and its haplotype at the putative promoter for IgA-specific receptor gene with IgA nephropathy among the Chinese Han population
Authors
Keywordsassociation
FCAR
IgA nephropathy
promoter
susceptibility
Issue Date2011
PublisherOxford University Press. The Journal's web site is located at http://ndt.oxfordjournals.org/
Citation
Nephrology Dialysis Transplantation, 2011, v. 26 n. 8, p. 2537-2544 How to Cite?
AbstractBackground. One-third to half of IgA nephropathy (IgAN) patients have raised serum IgA levels. Decreased clearance of IgA/IgA complex has been observed in IgAN patients. FCAR codes for IgA-specific receptor and plays an important role in IgA metabolism. Previous small sample-sized studies reported controversial findings in its association with IgAN.Methods. We re-sequenced the FCAR in 107 IgAN patients and 112 controls. Association of -27T/C and their haplotypes were performed in 606 patients versus 606 controls, its two independent subsets: 293 single patients with family members and 313 cases versus 606 controls. Functional impact of -27T>C and their haplotypes were analyzed by bioinformatics, allelic differential expression and luciferase activity assays. Cell surface FCAR density between -27T/C heterozygous patients and -27T/T homozygous controls was assessed by flow cytometry.Results. -27T>C, on the consensus TATA box of transcription factor-binding motif in the putative promoter of the gene was the only variation identified in all coding, splice-site and known protein-binding sequence in re-sequencing. -27C and its haplotype were associated with IgAN (P = 0.0034/0.0013, 0.0099/0.0054, 0.0129/0.0076 and 0.00039/0.00014 in 606 cases versus 606 controls, family-based study, 313 cases versus 606 controls and meta-analysis, respectively). Bioinformatics predicted 2 bp binding changes by -27C. Allelic differential expression and luciferase activity assays showed a reduced expression/activity by the associated haplotype/allele (P < 0.001). -27T/C heterozygous patients had a lower receptor density on cell surface compared to -27T/T homozygous controls (P < 0.001).Conclusions. Our results provide evidence for genetic variation at the putative promoter region of FCAR conferring susceptibility to IgAN, suggesting -27C and its haplotype may be causative for the susceptibility among the Chinese Han population. © 2011 The Author Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/142394
ISSN
2015 Impact Factor: 4.085
2015 SCImago Journal Rankings: 1.780
ISI Accession Number ID
Funding AgencyGrant Number
State 985 Project of China
National Natural Science Foundation of China30570869
30771013
China Medical Board of New York05-827
Guangdong Provincial Natural Science Foundation07001511
Funding Information:

The project was supported by the State 985 Project of China, the National Natural Science Foundation of China (30570869 and 30771013), China Medical Board of New York (05-827) and the Guangdong Provincial Natural Science Foundation (07001511). We thank Dr Miaoxin Li, Department of Psychiatry, University of Hong Kong, for checking the statistical analyses.

References

 

DC FieldValueLanguage
dc.contributor.authorHuang, Wen_HK
dc.contributor.authorGu, Hen_HK
dc.contributor.authorLi, Ren_HK
dc.contributor.authorLou, Ten_HK
dc.contributor.authorZhang, Jen_HK
dc.contributor.authorShi, Wen_HK
dc.contributor.authorYe, Zen_HK
dc.contributor.authorZhou, Yen_HK
dc.contributor.authorLi, Cen_HK
dc.contributor.authorXiong, Sen_HK
dc.contributor.authorLi, Len_HK
dc.contributor.authorWu, Cen_HK
dc.contributor.authorLeung, JCKen_HK
dc.contributor.authorLam, MFen_HK
dc.contributor.authorLai, KNen_HK
dc.contributor.authorWang, Yen_HK
dc.date.accessioned2011-10-28T02:45:01Z-
dc.date.available2011-10-28T02:45:01Z-
dc.date.issued2011en_HK
dc.identifier.citationNephrology Dialysis Transplantation, 2011, v. 26 n. 8, p. 2537-2544en_HK
dc.identifier.issn0931-0509en_HK
dc.identifier.urihttp://hdl.handle.net/10722/142394-
dc.description.abstractBackground. One-third to half of IgA nephropathy (IgAN) patients have raised serum IgA levels. Decreased clearance of IgA/IgA complex has been observed in IgAN patients. FCAR codes for IgA-specific receptor and plays an important role in IgA metabolism. Previous small sample-sized studies reported controversial findings in its association with IgAN.Methods. We re-sequenced the FCAR in 107 IgAN patients and 112 controls. Association of -27T/C and their haplotypes were performed in 606 patients versus 606 controls, its two independent subsets: 293 single patients with family members and 313 cases versus 606 controls. Functional impact of -27T>C and their haplotypes were analyzed by bioinformatics, allelic differential expression and luciferase activity assays. Cell surface FCAR density between -27T/C heterozygous patients and -27T/T homozygous controls was assessed by flow cytometry.Results. -27T>C, on the consensus TATA box of transcription factor-binding motif in the putative promoter of the gene was the only variation identified in all coding, splice-site and known protein-binding sequence in re-sequencing. -27C and its haplotype were associated with IgAN (P = 0.0034/0.0013, 0.0099/0.0054, 0.0129/0.0076 and 0.00039/0.00014 in 606 cases versus 606 controls, family-based study, 313 cases versus 606 controls and meta-analysis, respectively). Bioinformatics predicted 2 bp binding changes by -27C. Allelic differential expression and luciferase activity assays showed a reduced expression/activity by the associated haplotype/allele (P < 0.001). -27T/C heterozygous patients had a lower receptor density on cell surface compared to -27T/T homozygous controls (P < 0.001).Conclusions. Our results provide evidence for genetic variation at the putative promoter region of FCAR conferring susceptibility to IgAN, suggesting -27C and its haplotype may be causative for the susceptibility among the Chinese Han population. © 2011 The Author Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.en_HK
dc.languageengen_US
dc.publisherOxford University Press. The Journal's web site is located at http://ndt.oxfordjournals.org/en_HK
dc.relation.ispartofNephrology Dialysis Transplantationen_HK
dc.subjectassociationen_HK
dc.subjectFCARen_HK
dc.subjectIgA nephropathyen_HK
dc.subjectpromoteren_HK
dc.subjectsusceptibilityen_HK
dc.subject.meshAsian Continental Ancestry Group - genetics-
dc.subject.meshGlomerulonephritis, IGA - genetics-
dc.subject.meshHaplotypes - genetics-
dc.subject.meshPolymorphism, Single Nucleotide - genetics-
dc.subject.meshReceptors, Fc - genetics-
dc.titleAssociation of -27T>C and its haplotype at the putative promoter for IgA-specific receptor gene with IgA nephropathy among the Chinese Han populationen_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_subscribed_fulltext-
dc.identifier.doi10.1093/ndt/gfq765en_HK
dc.identifier.pmid21273231-
dc.identifier.scopuseid_2-s2.0-79961050762en_HK
dc.identifier.hkuros197014en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-79961050762&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume26en_HK
dc.identifier.issue8en_HK
dc.identifier.spage2537en_HK
dc.identifier.epage2544en_HK
dc.identifier.isiWOS:000293336500020-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridHuang, W=10041590500en_HK
dc.identifier.scopusauthoridGu, H=24173429900en_HK
dc.identifier.scopusauthoridLi, R=55491291300en_HK
dc.identifier.scopusauthoridLou, T=7004047319en_HK
dc.identifier.scopusauthoridZhang, J=49462077600en_HK
dc.identifier.scopusauthoridShi, W=49461944600en_HK
dc.identifier.scopusauthoridYe, Z=55449466000en_HK
dc.identifier.scopusauthoridZhou, Y=46261808600en_HK
dc.identifier.scopusauthoridLi, C=26663041900en_HK
dc.identifier.scopusauthoridXiong, S=26768403300en_HK
dc.identifier.scopusauthoridLi, L=36064664900en_HK
dc.identifier.scopusauthoridWu, C=35492144800en_HK
dc.identifier.scopusauthoridLeung, JCK=7202180349en_HK
dc.identifier.scopusauthoridLam, MF=35300050600en_HK
dc.identifier.scopusauthoridLai, KN=7402135706en_HK
dc.identifier.scopusauthoridWang, Y=36088373700en_HK
dc.identifier.citeulike9612656-

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