The Development of Atypical Haemolytic-uraemic Syndrome is Influenced by Susceptibility Factors in Factor H and Membrane Cofactor Protein: Evidence from Two Independent Cohorts

Overview

Journal J Med Genet

Specialty Genetics

Date 2005 Mar 24

PMID 15784724

Citations 58

Authors

V Fremeaux-Bacchi

E J Kemp

J A Goodship

M-A Dragon-Durey

L Strain

C Loirat

H-W Deng

T H J Goodship

Affiliations

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Abstract

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.

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