Genetic variation of DKK3 may modify renal disease severity in ADPKD
Ημερομηνία
2010Συγγραφέας
Liu, M.Shi, S.
Senthilnathan, S.
Yu, J.
Wu, E.
Bergmann, C.
Zerres, K.
Bogdanova, N.
Coto, E.
Constantinou-Deltas, Constantinos D.
Pierides, Alkis M.
Demetriou, Kyproula
Devuyst, O.
Gitomer, B.
Laakso, M.
Lumiaho, A.
Lamnissou, Klea
Magistroni, R.
Parfrey, P.
Breuning, M.
Peters, D. J. M.
Torra, R.
Winearls, C. G.
Torres, V. E.
Harris, Peter C.
Paterson, A. D.
Pei, Y.
ISSN
1046-6673Source
Journal of the American Society of NephrologyVolume
21Pages
1510-1520Google Scholar check
Keyword(s):
Metadata
Εμφάνιση πλήρους εγγραφήςΕπιτομή
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/β-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. Copyright © 2010 by the American Society of Nephrology.
Collections
Cite as
Related items
Showing items related by title, author, creator and subject.
-
Article
Renal graft outcome in autosomal dominant medullary cystic kidney disease type 1
Soloukides, Andreas P.; Moutzouris, Dimitrios Anestis D.; Papagregoriou, Gregory N.; Stavrou, Christoforos V.; Constantinou-Deltas, Constantinos D.; Tzanatos, Helen A. (2013)Background: Medullary cystic kidney disease (MCKD) is an inherited interstitial nephritis, leading to endstage renal disease (ESRD) between the fourth and seventh decade of life. MCKD shares clinical and morphological ...
-
Article
Outcome of kidney transplantation in autosomal dominant medullary cystic kidney disease type 1
Stavrou, Christoforos V.; Constantinou-Deltas, Constantinos D.; Christofides, Tasos C.; Pierides, Alkis M. (2003)Background. Autosomal dominant medullary cystic kidney disease (ADMCKD) is an inherited, distinct, chronic, tubulointerstitial, cystic-type nephropathy, often described together with juvenile nephronophthisis as a single ...
-
Article
Autosomal-dominant medullary cystic kidney disease type 1: Clinical and molecular findings in six large Cypriot familiesAAA
Stavrou, Christoforos V.; Koptides, Michael; Tombazos, C.; Psara, E.; Patsias, Charalambos; Zouvani, Ioanna; Kyriacou, Kyriacos C.; Hildebrandt, F.; Christofides, Tasos C.; Pierides, Alkis M.; Constantinou-Deltas, Constantinos D. (2002)Background. Autosomal-dominant medullary cystic kidney disease (ADMCKD), a hereditary chronic interstitial nephropathy, recently attracted attention because of the cloning or mapping of certain gene loci, namely NPHP1, ...