The development of atypical haemolytic-uraemic syndrome is influenced by susceptibility factors in factor H and membrane cofactor protein: evidence from two independent cohorts.
BACKGROUND
In both familial and sporadic atypical haemolytic-uraemic syndrome (aHUS), mutations have been reported in regulators of the alternative complement pathway including factor H (CFH), membrane cofactor protein (MCP), and the serine protease factor I (IF). A characteristic feature of both MCP and CFH associated HUS is reduced penetrance and variable inheritance; one possible explanation for this is that functional changes in complement proteins act as modifiers.


OBJECTIVE
To examine single nucleotide polymorphisms in both CFH and MCP genes in two large cohorts of HUS patients (Newcastle and Paris).


RESULTS
In both cohorts there was an association with HUS for both CFH and MCP alleles. CFH and MCP haplotypes were also significantly different in HUS patients compared with controls.


CONCLUSIONS
This study suggests that there are naturally occurring susceptibility factors in CFH and MCP for the development of atypical HUS.
Fremeaux-Bacchi
V
V
Service d'Immunologie Biologique, Hôpital Européen Georges Pompidou, Paris, France.
Kemp
E J
EJ
Goodship
J A
JA
Dragon-Durey
M-A
MA
Strain
L
L
Loirat
C
C
Deng
H-W
HW
Goodship
T H J
TH
D000483:Alleles; D015331:Cohort Studies; D017242:Complement Factor H / Q000235:genetics* / Q000378:metabolism; D003165:Complement System Proteins; D017931:DNA Primers / Q000737:chemistry; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006463:Hemolytic-Uremic Syndrome / Q000175:diagnosis* / Q000235:genetics*; D006801:Humans; D051916:Membrane Cofactor Protein / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D011951:Receptors, Complement
D017931:DNA Primers; D051916:Membrane Cofactor Protein; D011951:Receptors, Complement; D017242:Complement Factor H; D003165:Complement System Proteins