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Allelic Variants of Complement Genes Associated with Dense Deposit Disease
Journal article   Open access

Allelic Variants of Complement Genes Associated with Dense Deposit Disease

Maria Asuncion Abrera-Abeleda, Carla Nishimura, Kathy Frees, Michael Jones, Tara Maga, Louis M Katz, Yuzhou Zhang and Richard J.H Smith
Journal of the American Society of Nephrology, Vol.22(8), pp.1551-1559
08/2011
DOI: 10.1681/ASN.2010080795
PMCID: PMC3148710
PMID: 21784901
url
https://doi.org/10.1681/ASN.2010080795View
Published (Version of record) Open Access

Abstract

The alternative pathway of the complement cascade plays a role in the pathogenesis of dense deposit disease (DDD). Deficiency of complement factor H and mutations in CFH associate with the development of DDD, but it is unknown whether allelic variants in other complement genes also associate with this disease. We studied patients with DDD and identified previously unreported sequence alterations in several genes in addition to allelic variants and haplotypes common to patients with DDD. We found that the likelihood of developing DDD increases with the presence of two or more risk alleles in CFH and C3 . To determine the functional consequence of this finding, we measured the activity of the alternative pathway in serum samples from phenotypically normal controls genotyped for variants in CFH and C3 . Alternative pathway activity was higher in the presence of variants associated with DDD. Taken together, these data confirm that DDD is a complex genetic disease and may provide targets for the development of disease-specific therapies.
Clinical Research

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