Display Settings:

Format

Send to:

Choose Destination
We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
J Am Soc Nephrol. 2010 Sep;21(9):1510-20. doi: 10.1681/ASN.2010030237. Epub 2010 Jul 8.

Genetic variation of DKK3 may modify renal disease severity in ADPKD.

Author information

  • 1Program in Genetics and Genome Biology, Hospital for Sick Children, Toronto, Ontario, Canada.

Abstract

Significant variation in the course of autosomal dominant polycystic kidney disease ( ADPKD) within families suggests the presence of effect modifiers. Recent studies of the variation within families harboring PKD1 mutations indicate that genetic background may account for 32 to 42% of the variance in estimated GFR (eGFR) before ESRD and 43 to 78% of the variance in age at ESRD onset, but the genetic modifiers are unknown. Here, we conducted a high-throughput single-nucleotide polymorphism (SNP) genotyping association study of 173 biological candidate genes in 794 white patients from 227 families with PKD1. We analyzed two primary outcomes: (1) eGFR and (2) time to ESRD (renal survival). For both outcomes, we used multidimensional scaling to correct for population structure and generalized estimating equations to account for the relatedness among individuals within the same family. We found suggestive associations between each of 12 SNPs and at least one of the renal outcomes. We genotyped these SNPs in a second set of 472 white patients from 229 families with PKD1 and performed a joint analysis on both cohorts. Three SNPs continued to show suggestive/significant association with eGFR at the Dickkopf 3 (DKK3) gene locus; no SNPs significantly associated with renal survival. DKK3 antagonizes Wnt/beta-catenin signaling, which may modulate renal cyst growth. Pending replication, our study suggests that genetic variation of DKK3 may modify severity of ADPKD resulting from PKD1 mutations.

PMID:
20616171
[PubMed - indexed for MEDLINE]
PMCID:
PMC3013521
Free PMC Article

Images from this publication.See all images (2)Free text

Figure 1.
Figure 2.
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Write to the Help Desk