Common genetic variants in complement genes other than CFH, CD46 and the CFHRs are not associated with aHUS

Luca Ermini; Timothy H.J. Goodship; Lisa Strain; Michael E. Weale; Steven H. Sacks; Heather J. Cordell; Veronique Fremeaux-Bacchi; Neil S. Sheerin

doi:10.1016/j.molimm.2011.11.003

Common genetic variants in complement genes other than CFH, CD46 and the CFHRs are not associated with aHUS

Luca Ermini, Timothy H.J. Goodship, Lisa Strain, Michael E. Weale, Steven H. Sacks, Heather J. Cordell, Veronique Fremeaux-Bacchi, Neil S. Sheerin^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Research › peer-review

35 Citations (Scopus)

Abstract

It is well established that common genetic variants in CFH, CD46 and the CFHRs are additional risk factors for the development of aHUS. To examine the hypothesis that common variants in other complement genes have a similar effect we genotyped 501 SNPs in 47 complement genes in 94 aHUS patients from Newcastle, 126 aHUS patients from Paris, 374 UK controls and 165 French controls. We replicated the associations in CFH, CD46 and the CFHRs but found no association with any other complement gene. The strongest associations replicated in both cohorts were found for four SNPs within CD46 (p-value<10^-3) and five SNPs within CFH (p-value<5×10^-3). Significant replicable associations with single SNPs in CFHR2, CFHR4 and an intergenic SNP (CR1-CD46) were also found. Analysis of the Paris cohort showed that the association with CD46 SNPs was only present in those patients with complement mutations. Haplotype analysis showed at-risk and protective haplotypes in both CD46 and CFH. The CD46 haplotype was only disease-associated in those patients with mutations.

Original language	English
Pages (from-to)	640-648
Number of pages	9
Journal	Molecular Immunology
Volume	49
Issue number	4
DOIs	https://doi.org/10.1016/j.molimm.2011.11.003
Publication status	Published - Jan 2012
Externally published	Yes

Keywords

AHUS
Complement
Genetic polymorphisms

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10.1016/j.molimm.2011.11.003

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title = "Common genetic variants in complement genes other than CFH, CD46 and the CFHRs are not associated with aHUS",

abstract = "It is well established that common genetic variants in CFH, CD46 and the CFHRs are additional risk factors for the development of aHUS. To examine the hypothesis that common variants in other complement genes have a similar effect we genotyped 501 SNPs in 47 complement genes in 94 aHUS patients from Newcastle, 126 aHUS patients from Paris, 374 UK controls and 165 French controls. We replicated the associations in CFH, CD46 and the CFHRs but found no association with any other complement gene. The strongest associations replicated in both cohorts were found for four SNPs within CD46 (p-value<10-3) and five SNPs within CFH (p-value<5×10-3). Significant replicable associations with single SNPs in CFHR2, CFHR4 and an intergenic SNP (CR1-CD46) were also found. Analysis of the Paris cohort showed that the association with CD46 SNPs was only present in those patients with complement mutations. Haplotype analysis showed at-risk and protective haplotypes in both CD46 and CFH. The CD46 haplotype was only disease-associated in those patients with mutations.",

keywords = "AHUS, Complement, Genetic polymorphisms",

author = "Luca Ermini and Goodship, {Timothy H.J.} and Lisa Strain and Weale, {Michael E.} and Sacks, {Steven H.} and Cordell, {Heather J.} and Veronique Fremeaux-Bacchi and Sheerin, {Neil S.}",

note = "Funding Information: This study was supported by grant provided by the Medical Research Council ( G0701325 ). The funding source had no involvement in study design; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication. Funding Information: We acknowledge use of DNA from The UK Blood Services collection of Common Controls (UKBS collection), funded by the Wellcome Trust grant 076113/C/04/Z , by the Juvenile Diabetes Research Foundation grant WT061858 , and by the National Institute of Health Research of England . The collection was established as part of the Wellcome Trust Case-Control Consortium. ",

year = "2012",

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doi = "10.1016/j.molimm.2011.11.003",

language = "English",

volume = "49",

pages = "640--648",

journal = "Molecular Immunology",

issn = "0161-5890",

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T1 - Common genetic variants in complement genes other than CFH, CD46 and the CFHRs are not associated with aHUS

AU - Ermini, Luca

AU - Goodship, Timothy H.J.

AU - Strain, Lisa

AU - Weale, Michael E.

AU - Sacks, Steven H.

AU - Cordell, Heather J.

AU - Fremeaux-Bacchi, Veronique

AU - Sheerin, Neil S.

N1 - Funding Information: This study was supported by grant provided by the Medical Research Council ( G0701325 ). The funding source had no involvement in study design; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication. Funding Information: We acknowledge use of DNA from The UK Blood Services collection of Common Controls (UKBS collection), funded by the Wellcome Trust grant 076113/C/04/Z , by the Juvenile Diabetes Research Foundation grant WT061858 , and by the National Institute of Health Research of England . The collection was established as part of the Wellcome Trust Case-Control Consortium.

PY - 2012/1

Y1 - 2012/1

N2 - It is well established that common genetic variants in CFH, CD46 and the CFHRs are additional risk factors for the development of aHUS. To examine the hypothesis that common variants in other complement genes have a similar effect we genotyped 501 SNPs in 47 complement genes in 94 aHUS patients from Newcastle, 126 aHUS patients from Paris, 374 UK controls and 165 French controls. We replicated the associations in CFH, CD46 and the CFHRs but found no association with any other complement gene. The strongest associations replicated in both cohorts were found for four SNPs within CD46 (p-value<10-3) and five SNPs within CFH (p-value<5×10-3). Significant replicable associations with single SNPs in CFHR2, CFHR4 and an intergenic SNP (CR1-CD46) were also found. Analysis of the Paris cohort showed that the association with CD46 SNPs was only present in those patients with complement mutations. Haplotype analysis showed at-risk and protective haplotypes in both CD46 and CFH. The CD46 haplotype was only disease-associated in those patients with mutations.

AB - It is well established that common genetic variants in CFH, CD46 and the CFHRs are additional risk factors for the development of aHUS. To examine the hypothesis that common variants in other complement genes have a similar effect we genotyped 501 SNPs in 47 complement genes in 94 aHUS patients from Newcastle, 126 aHUS patients from Paris, 374 UK controls and 165 French controls. We replicated the associations in CFH, CD46 and the CFHRs but found no association with any other complement gene. The strongest associations replicated in both cohorts were found for four SNPs within CD46 (p-value<10-3) and five SNPs within CFH (p-value<5×10-3). Significant replicable associations with single SNPs in CFHR2, CFHR4 and an intergenic SNP (CR1-CD46) were also found. Analysis of the Paris cohort showed that the association with CD46 SNPs was only present in those patients with complement mutations. Haplotype analysis showed at-risk and protective haplotypes in both CD46 and CFH. The CD46 haplotype was only disease-associated in those patients with mutations.

KW - AHUS

KW - Complement

KW - Genetic polymorphisms

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SN - 0161-5890

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EP - 648

JO - Molecular Immunology

JF - Molecular Immunology

IS - 4

ER -

Common genetic variants in complement genes other than CFH, CD46 and the CFHRs are not associated with aHUS

Abstract

Keywords

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