van der Zanden, LFM;
van Rooij, IALM;
Quaedackers, JSLT;
Nijman, RJM;
Steffens, M;
de Wall, LLL;
Bongers, EMHF;
... Feitz, WFJ; + view all
(2021)
CDH12 as a Candidate Gene for Kidney Injury in Posterior Urethral Valve Cases: A Genome-wide Association Study Among Patients with Obstructive Uropathies.
European Urology Open Science
, 28
pp. 26-35.
10.1016/j.euros.2021.04.001.
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Abstract
Background: Posterior urethral valves (PUVs) and ureteropelvic junction obstruction (UPJO) are congenital obstructive uropathies that may impair kidney development. Objective: To identify genetic variants associated with kidney injury in patients with obstructive uropathy. Design, setting, and participants: We included 487 patients born in 1981 or later who underwent pyeloplasty or valve resection before 18 yr of age in the discovery phase, 102 PUV patients in a first replication phase, and 102 in a second replication phase. Outcome measurements and statistical analysis: Signs of kidney injury were defined as dialysis, nephrectomy, kidney transplantation, estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m , high blood pressure, antihypertensive medication use, proteinuria, and/or one kidney functioning at <45%. We used χ tests to calculate p values and odds ratios for >600 000 single-nucleotide polymorphisms (SNPs) in the discovery sample comparing patients with and without signs of kidney injury within 5 yr after surgery. We performed stratified analyses for PUV and UPJO and Kaplan-Meier and Cox regression analyses in the discovery and two replication samples for the associated SNPs, and RNA and protein expression analyses for the associated gene in fetal tissues. Results and limitations: Despite the small and nonhomogeneous sample, we observed suggestive associations for six SNPs in three loci, of which rs6874819 in the CDH12 gene was the most clear (p = 7.5 × 10 ). This SNP also seemed to be associated with time to kidney injury in the PUV discovery and replication samples. RNA expression analyses showed clear CDH12 expression in fetal kidneys, which was confirmed by protein immunolocalization. Conclusions: This study identified CDH12 as a candidate gene for kidney injury in PUV. Patient summary: We found that variants of the CDH12 gene increase the risk of kidney injury in patients with extra flaps of tissue in the urethra (posterior urethral valves). This is the first report on this gene in this context. Our study provides interesting new information about the pathways involved and important leads for further research for this condition. 2 2 –7
| Type: | Article |
|---|---|
| Title: | CDH12 as a Candidate Gene for Kidney Injury in Posterior Urethral Valve Cases: A Genome-wide Association Study Among Patients with Obstructive Uropathies |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.euros.2021.04.001 |
| Publisher version: | http://doi.org/10.1016/j.euros.2021.04.001 |
| Language: | English |
| Additional information: | This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Developmental Biology and Cancer Dept |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10127759 |
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