Association of angiotensin type 2 receptor gene polymorphisms with ureteropelvic junction obstruction in Brazilian patients

Abstract

Our results support that the AGTR2 gene may contribute to the pathogenesis of UPJO and the genetic origin of CAKUT could vary according to phenotype expression.

Genetic, environmental, and epigenetic factors involved in CAKUT

“…Single gene-based association studies found polymorphisms in MMP3, BMP4, and AGTR2 to be associated with an increased risk of CAKUT. [86][87][88] High-throughput genotyping technologies allow the rapid genotyping of >1 million SNPs across the whole genome and enable genome-wide association studies (GWAS) in a hypothesis free, unbiased manner. The only study to date that has exploited these advantages conducted a genome-wide TDT analysis in 410 patient-parent trios from Ireland using 643,691 SNPs, as well as a GWAS in 500 unrelated patients with VUR and 851 controls using 580,000 SNPs.…”

Congenital anomalies of the kidney and urinary tract: An embryogenetic review

“…The frequency of the G allele in AGTR2 gene was also higher in CAKUT patients than in the general population in Italian (Rigoli et al, ) and Korean children (Hahn et al, ), while no differences were found in patients from Greece (Siomou et al, ). In this context, our group extended previous findings by increasing the sample size (290 cases and 262 controls) and by testing five SNPs that cover the entire AGTR2 gene (Miranda et al, ). A significant association of AGTR2 gene at rs3736556 and at rs5194 with UPJO were found, while no associations were detected with MCDK and vesicoureteral reflux (VUR) in our Brazilian sample (Miranda et al, ).…”

“…In this context, our group extended previous findings by increasing the sample size (290 cases and 262 controls) and by testing five SNPs that cover the entire AGTR2 gene (Miranda et al, ). A significant association of AGTR2 gene at rs3736556 and at rs5194 with UPJO were found, while no associations were detected with MCDK and vesicoureteral reflux (VUR) in our Brazilian sample (Miranda et al, ).…”

“…One is the regulation of apoptosis of the undifferentiated mesenchymal cells surrounding the developing ureter. A second role is the inhibition of ectopic ureteral budding (Yosypiv et al, ; Song et al, ; Miranda et al, ). The general hypothesis is that abnormalities in the expression of AT 2 receptors hinder interaction between the UB and metanephric blastema, and hamper normal development, resulting in CAKUT (Yosypiv, ).…”

“…Currently, the genes BMP4 (bone morphogenetic protein 4; Miyazaki et al, 2000;Hoshino et al, 2008;Weber et al, 2008a;Chi et al, 2011;Paces-Fessy et al, 2012;Dos Reis et al, 2014), AGTR2 (angiotensin II receptor type 2; Nishimura et al, 1999;Oshima et al, 2001;Nakanishi and Yoshikawa, 2003;Hahn et al, 2005;Miranda et al, 2014), PAX2 (paired box gene 2; Dressler et al, 1993;Nakanishi and Yoshikawa, 2003;Dziarmaga et al, 2006;Chen et al, 2008;Harshman and Brophy, 2012;de Miranda et al, 2014), SIX1 (Ruf et al, 2004), SIX5 (Hoskins et al, 2007), GDNF (glial cell line-derived neurotrophic factor), RET (Rearranged during Tranfection), WNT (wingless-type MMTV integration site family), SALL (Spalt-like transcription factor; Nishinakamura et al, 2001;Nishinakamura and Takasato, 2005), EYA1 (Eyes Absent 1; Abdelhak et al, 1997), TCF2 (transcription factor 2; Weber et al, 2006;Decramer et al, 2007), and others are believed to play a role in the pathogenesis of human CAKUT, as shown in Table 1. Possibly, the failure of signaling events elicited by these genes at specified times results in diverse phenotypes of CAKUT (Sax en and Sariola, 1987;Dressler et al, 1990;Nishimura et al, 1999;Ichikawa et al, 2002;Kuwayama et al, 2002;Yosypiv, 2012Yosypiv, , 2008Marrone and Ho, 2014).…”