Insertion/Deletion Polymorphisms in the ΔNp63 Promoter Are a Risk Factor for Bladder Exstrophy Epispadias Complex

• DOI: 10.1371/journal.pgen.1003070
• Publication Date: 2012-12-20T21:37:33Z
• Authors: Simon Wilkins; Ke Wei Zhang; Istiak Mahfuz; Renaud Quantin; Nancy D'Cruz; John Hutson; Michael Ee; Darius Bagli; Karen Aitken; Fion Nga-Yin Fong; Patrick Kwok-Shin...; Stephen Kwok-Wing...; Wendy Yin-Wan Fung; Tahmina Banu; Atul Thakre; Kaid Johar; Enrique Jaureguizar; Long Li; Wei Cheng
• Keywords: Indel

Bladder exstrophy epispadias complex (BEEC) is a severe congenital anomaly; however, the genetic and molecular mechanisms underlying formation of BEEC remain unclear. TP63, member TP53 tumor suppressor gene family, expressed in bladder urothelium skin over external genitalia during mammalian development. It plays role We have previously shown that p63(-/-) mouse embryos developed phenotype identical to human BEEC. hypothesised TP63 involved pathogenesis. RNA was extracted from foreskin specimens and, as mice, ΔNp63 predominant p63 isoform. expression epithelium patients reduced. DNA sequenced 163 285 ethnicity-matched controls. No exon mutations were detected. Sequencing promoter showed 7 single nucleotide polymorphisms 4 insertion/deletion (indel) polymorphisms. Indel associated with an increased risk Significantly sites indel differed between Caucasian non-Caucasian populations. A 12-base-pair deletion only (p = 0.0052 Odds Ratio (OR) 18.33), whereas 4-base-pair insertion 0.0259 OR 4.583). found consistent statistically significant reduction transcriptional efficiencies sequences containing luciferase assays. These findings suggest lead expression, which could