Allelic variants of complement genes associated with dense deposit disease.
J Am Soc Nephrol
; 22(8): 1551-9, 2011 Aug.
Article
em En
| MEDLINE
| ID: mdl-21784901
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.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Variação Genética
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Proteínas do Sistema Complemento
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Glomerulonefrite Membranoproliferativa
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Alelos
Tipo de estudo:
Etiology_studies
/
Prognostic_studies
Limite:
Adolescent
/
Adult
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Female
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Humans
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Male
Idioma:
En
Revista:
J Am Soc Nephrol
Assunto da revista:
NEFROLOGIA
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Estados Unidos