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.
authors.affiliation: Institute of Cellular Medicine, Newcastle University, Framlington Place, Newcastle upon Tyne NE2 4HH, United Kingdom.
authors.forename: Luca
authors.initials: L
authors.lastname: Ermini
authors.forename: Timothy H J
authors.initials: TH
authors.lastname: Goodship
authors.forename: Lisa
authors.initials: L
authors.lastname: Strain
authors.forename: Michael E
authors.initials: ME
authors.lastname: Weale
authors.forename: Steven H
authors.initials: SH
authors.lastname: Sacks
authors.forename: Heather J
authors.initials: HJ
authors.lastname: Cordell
authors.forename: Veronique
authors.initials: V
authors.lastname: Fremeaux-Bacchi
authors.forename: Neil S
authors.initials: NS
authors.lastname: Sheerin
mesh_terms: D000328:Adult; D001053:Apolipoproteins / Q000235:genetics*; D016022:Case-Control Studies; D015331:Cohort Studies; D003176:Complement C3 / Q000235:genetics; D017242:Complement Factor H / Q000235:genetics*; D017244:Complement Factor I / Q000235:genetics; D003165:Complement System Proteins / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006463:Hemolytic-Uremic Syndrome / Q000235:genetics*; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D051916:Membrane Cofactor Protein / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D044465:White People; D055815:Young Adult
chemical_list: D001053:Apolipoproteins; C105092:CFHR4 protein, human; D003176:Complement C3; D051916:Membrane Cofactor Protein; D017242:Complement Factor H; D003165:Complement System Proteins; C493611:CFI protein, human; D017244:Complement Factor I