title: Candidate gene association study implicates p63 in the etiology of nonsyndromic bladder-exstrophy-epispadias complex.
abstract: BACKGROUND
  Bladder-exstrophy-epispadias complex (BEEC) is a severe congenital anomaly that represents a spectrum of urological abnormalities where parts or all of the distal urinary tract fail to close during development. Multiple lines of evidence strongly suggested p63 as a plausible candidate gene. We conducted a candidate gene association study to further investigate the role of p63 in human BEEC.
  
  
  METHODS
  We conducted a family-based association study of p63 using 154 Caucasian patients with nonsyndromic BEEC and their unaffected parents. High throughput single nucleotide polymorphism (SNP) genotyping was carried out using Illumina's Golden Gate Assay for 109 selected tagging SNPs localized within p63 with a minor allele frequency > 0.01. Individual and haplotype SNP transmission disequilibrium tests were conducted using Plink and Haploview, respectively. We also examined parent-of-origin effects using paternal asymmetry tests implemented in FAMHAP (http://famhap.meb.uni-bonn.de/index.html).
  
  
  RESULTS
  Nominally significant associations were identified between BEEC and six SNPs (rs17447782, rs1913720, rs6790167, rs9865857, rs1543969, rs4687100), and four haplotype blocks including or near these significant SNPs. Analysis of parent-of-origin effects showed significant results for seven SNPs (rs4118375, rs12696596, rs6779677, rs13091309, rs7642420, rs1913721, and rs1399774). None of these results remained significant after multiple testing correction.
  
  
  CONCLUSIONS
  The altered transmission of p63 variants in nonsyndromic BEEC patients may be suggestive of its involvement in the disease etiology. Further and large multi-institutional collaborative studies are required to elucidate the role of p63 in nonsyndromic BEEC.
authors.affiliation: Department of Public Health Sciences, School of Medicine, University of California, Davis, California.
authors.forename: Lihong
authors.initials: L
authors.lastname: Qi
authors.forename: Mei
authors.initials: M
authors.lastname: Wang
authors.forename: Garima
authors.initials: G
authors.lastname: Yagnik
authors.forename: Manuel
authors.initials: M
authors.lastname: Mattheisen
authors.forename: John P
authors.initials: JP
authors.lastname: Gearhart
authors.forename: Yegappan
authors.initials: Y
authors.lastname: Lakshmanan
authors.forename: Anne-Karolin
authors.initials: AK
authors.lastname: Ebert
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Rösch
authors.forename: Michael
authors.initials: M
authors.lastname: Ludwig
authors.forename: Markus
authors.initials: M
authors.lastname: Draaken
authors.forename: Heiko
authors.initials: H
authors.lastname: Reutter
authors.forename: Simeon A
authors.initials: SA
authors.lastname: Boyadjiev
mesh_terms: D058070:Asymptomatic Diseases; D001746:Bladder Exstrophy / Q000150:complications / Q000235:genetics* / Q000473:pathology; D004842:Epispadias / Q000150:complications / Q000235:genetics* / Q000473:pathology; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D006239:Haplotypes; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D040582:Inheritance Patterns; D015810:Linkage Disequilibrium; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D001743:Urinary Bladder / Q000378:metabolism* / Q000473:pathology
chemical_list: C081876:CKAP4 protein, human; D008565:Membrane Proteins
keywords: BEEC; association study; bladder exstrophy; candidate gene; case-parent trio; epispadias; p63