ArticlePLoS genetics2012
Insertion/deletion polymorphisms in the ΔNp63 promoter are a risk factor for bladder exstrophy epispadias complex.
Article in PLoS genetics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 106 citations in OpenAlex.
- Genome-wide association study and meta-analysis identify ISL1 as genome-wide significant susceptibility gene for bladder exstrophy.PLoS genetics · 2015Pooled it
- Mutations Upstream of ppp2ca Affect Body Weight in Asian Seabass.Marine biotechnology (New York, N.Y.) · 2025Article
- Ventral body wall closure: Mechanistic insights from mouse models and translation to human pathology.Developmental dynamics : an official publication of the American Association of Anatomists · 2025Review
- Pathophysiology of Congenital Anomalies of the Kidney and Urinary Tract: A Comprehensive Review.Cells · 2024Review
- Bladder exstrophy-epispadias-cloacal exstrophy complex: characteristics, aetiologies, and epidemiologic findings.African urology · 2024Article
- Review
- Roles for urothelium in normal and aberrant urinary tract development.Nature reviews. Urology · 2020Review
- Identification of an enhancer region within the TP63/LEPREL1 locus containing genetic variants associated with bladder cancer risk.Cellular oncology (Dordrecht, Netherlands) · 2018Article
- Clinical and risk factor analysis of cloacal defects in the National Birth Defects Prevention Study.American journal of medical genetics. Part A · 2017Article
- Role of the LF-SINE-Derived DistalJournal of pediatric genetics · 2017Article
- ISL1 is a major susceptibility gene for classic bladder exstrophy and a regulator of urinary tract development.Scientific reports · 2017Article
- Genetics of Bladder-Exstrophy-Epispadias Complex (BEEC): Systematic Elucidation of Mendelian and Multifactorial Phenotypes.Current genomics · 2016Article
- Genome-wide association study and mouse expression data identify a highly conserved 32 kb intergenic region between WNT3 and WNT9b as possible susceptibility locus for isolated classic exstrophy of the bladder.Human molecular genetics · 2014Article
- Malformation syndromes associated with disorders of sex development.Nature reviews. Endocrinology · 2014Review
- Genetics of human congenital urinary bladder disease.Pediatric nephrology (Berlin, Germany) · 2014Review
- Modern management of the exstrophy-epispadias complex.Surgery research and practice · 2014Review
- Cytokeratin 15 marks basal epithelia in developing ureters and is upregulated in a subset of urothelial cell carcinomas.PloS one · 2013Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
19 authors at 10 institutions in 6 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Bladder exstrophy epispadias complex (BEEC) is a severe congenital anomaly; however, the genetic and molecular mechanisms underlying the formation of BEEC remain unclear. TP63, a member of TP53 tumor suppressor gene family, is expressed in bladder urothelium and skin over the external genitalia during mammalian development. It plays a role in bladder development. We have previously shown that p63(-/-) mouse embryos developed a bladder exstrophy phenotype identical to human BEEC. We hypothesised that TP63 is involved in human BEEC pathogenesis. RNA was extracted from BEEC foreskin specimens and, as in mice, ΔNp63 was the predominant p63 isoform. ΔNp63 expression in the foreskin and bladder epithelium of BEEC patients was reduced. DNA was sequenced from 163 BEEC patients and 285 ethnicity-matched controls. No exon mutations were detected. Sequencing of the ΔNp63 promoter showed 7 single nucleotide polymorphisms and 4 insertion/deletion (indel) polymorphisms. Indel polymorphisms were associated with an increased risk of BEEC. Significantly the sites of indel polymorphisms differed between Caucasian and non-Caucasian populations. A 12-base-pair deletion was associated with an increased risk with only Caucasian patients (p = 0.0052 Odds Ratio (OR) = 18.33), whereas a 4-base-pair insertion was only associated with non-Caucasian patients (p = 0.0259 OR = 4.583). We found a consistent and statistically significant reduction in transcriptional efficiencies of the promoter sequences containing indel polymorphisms in luciferase assays. These findings suggest that indel polymorphisms of the ΔNp63 promoter lead to a reduction in p63 expression, which could lead to BEEC.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.