title: PAX2 polymorphisms and congenital abnormalities of the kidney and urinary tract in a Brazilian pediatric population: evidence for a role in vesicoureteral reflux.
abstract: OBJECTIVE
  Congenital anomalies of the kidney and urinary tract (CAKUT) are common genetic malformations. Since the PAX2 gene has a role in kidney organogenesis, this study investigated the association of PAX2 gene polymorphisms with CAKUT in general and with specific phenotypes of CAKUT in a Brazilian pediatric population.
  
  
  METHODS
  This study included 241 individuals with antenatal hydronephrosis and 259 healthy controls. For genotyping and allelic discrimination we used the probes to rs2077642, rs4244341, rs6421335, rs11190698, and rs11190693.
  
  
  RESULTS
  No statistical differences in allele and genotype frequencies were observed for the single nucleotide polymorphism (SNP) rs11190693. At the SNPs rs4244341 and rs11190698, the frequencies of the ancestral alleles were significantly higher among CAKUT patients (rs4244341 allele G: 0.86 vs. 0.78; rs11190698 allele A: 0.85 vs. 0.79). At the SNP rs4244341, the genotype GG was increased in CAKUT group (0.72 vs. 0.61, P = 0.013), while the TT was higher in controls (0.01 vs. 0.05, P = 0.001). At the SNP rs11190698, the genotype CC was increased in controls (0.02 vs. 0.06, P = 0.01). The most frequent CAKUT phenotypes were vesicoureteral reflux (VUR), multicystic dysplastic kidney (MCDK), and ureteropelvic junction obstruction (UPJO). In patients with VUR, the frequencies of the monozygotic ancestral alleles decreased at the SNP rs11190693 (AA 0.13 vs. 0.26, P = 0.04) and increased at the SNP rs4244341 (GG 0.77 vs. 0.61, P = 0.03). No statistical differences were detected between controls and patients with UPJO and with MCDK for all SNPs.
  
  
  CONCLUSIONS
  The PAX2 gene seems to be involved with the pathogenesis of VUR in our sample.
authors.affiliation: National Institute of Science and Technology, Molecular Medicine (INCT-MM), Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Brazil.
authors.forename: Débora Marques
authors.initials: DM
authors.lastname: de Miranda
authors.forename: Augusto César Soares
authors.initials: AC
authors.lastname: Dos Santos Júnior
authors.forename: Geisilaine Soares
authors.initials: GS
authors.lastname: Dos Reis
authors.forename: Izabella Silva
authors.initials: IS
authors.lastname: Freitas
authors.forename: Thiago Guimarães Rosa
authors.initials: TG
authors.lastname: Carvalho
authors.forename: Luiz Armando Cunha
authors.initials: LA
authors.lastname: de Marco
authors.forename: Eduardo Araújo
authors.initials: EA
authors.lastname: Oliveira
authors.forename: Ana Cristina
authors.initials: AC
authors.lastname: Simões E Silva
mesh_terms: D002648:Child; D002675:Child, Preschool; D005260:Female; D005838:Genotype; D006801:Humans; D006869:Hydronephrosis / Q000151:congenital* / Q000473:pathology; D007223:Infant; D007668:Kidney / Q000473:pathology*; D008297:Male; D021782:Multicystic Dysplastic Kidney / Q000473:pathology*; D051762:PAX2 Transcription Factor / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D014517:Ureteral Obstruction / Q000473:pathology*; D014551:Urinary Tract / Q000473:pathology*; D014718:Vesico-Ureteral Reflux / Q000503:physiopathology*
chemical_list: D051762:PAX2 Transcription Factor; C497318:PAX2 protein, human