Lack of association between polymorphisms in C4b-binding protein and atypical haemolytic uraemic syndrome in the Spanish population
Open Access
- 29 October 2008
- journal article
- research article
- Published by Oxford University Press (OUP) in Clinical and Experimental Immunology
- Vol. 155 (1), 59-64
- https://doi.org/10.1111/j.1365-2249.2008.03798.x
Abstract
Summary: Dysregulation of the alternative pathway of complement activation, caused by mutations or polymorphisms in the genes encoding factor H, membrane co-factor protein, factor I or factor B, is associated strongly with predisposition to atypical haemolytic uraemic syndrome (aHUS). C4b-binding protein (C4BP), a major regulator of the classical pathway of complement activation, also has capacity to regulate the alternative pathway. Interestingly, the C4BP polymorphism p.Arg240His has been associated recently with predisposition to aHUS and the risk allele His240 showed decreased capacity to regulate the alternative pathway. Identification of novel aHUS predisposition factors has important implications for diagnosis and treatment in a significant number of aHUS patients; thus, we sought to replicate these association studies in an independent cohort of aHUS patients. In this study we show that the C4BP His240 allele corresponds to the C4BP*2 allele identified previously by isoelectric focusing in heterozygosis in 1·9–3·7% of unrelated Caucasians. Crucially, we found no differences between 102 unrelated Spanish aHUS patients and 128 healthy age-matched Spanish controls for the frequency of carriers of the His240 C4BP allele. This did not support an association between the p.Arg240His C4BP polymorphism and predisposition to aHUS in the Spanish population. In a similar study, we also failed to sustain an association between C4BP polymorphisms and predisposition to age-related macular degeneration, another disorder which is associated strongly with polymorphisms in factor H, and is thought to involve alternative pathway dysregulation.Keywords
This publication has 41 references indexed in Scilit:
- Translational Mini-Review Series on Complement Factor H: Genetics and disease associations of human complement factor HClinical and Experimental Immunology, 2007
- Progress in defining the molecular biology of age related macular degenerationHuman Genetics, 2007
- Deletion of Complement Factor H–Related Genes CFHR1 and CFHR3 Is Associated with Atypical Hemolytic Uremic SyndromePLoS Genetics, 2007
- Protective or aggressive: Paradoxical role of C3 in atypical hemolytic uremic syndromeMolecular Immunology, 2007
- Gain-of-function mutations in complement factor B are associated with atypical hemolytic uremic syndromeProceedings of the National Academy of Sciences, 2007
- Atypical Haemolytic Uraemic Syndrome Associated with a Hybrid Complement GenePLoS Medicine, 2006
- The development of atypical haemolytic-uraemic syndrome is influenced by susceptibility factors in factor H and membrane cofactor protein: evidence from two independent cohortsJournal of Medical Genetics, 2005
- CCP1–4 of the C4b-binding protein α-chain are required for factor I mediated cleavage of complement factor C3bMolecular Immunology, 2003
- Structure of the gene coding for the alpha polypeptide chain of the human complement component C4b-binding protein.The Journal of Experimental Medicine, 1991
- Protein S binding in relation to the subunit composition of human C4b‐binding proteinFEBS Letters, 1989