Miranda Debora M, Dos Santos Augusto Cesar, Sarubi Helena C, Bastos-Rodrigues Luciana, Rosa Daniela Valadão, Freitas Izabella S, De Marco Luiz Armando, Oliveira Eduardo A, Simões e Silva Ana Cristina
INCT/MM - National Institute of Science and Technology in Molecular Medicine, Federal University of Minas Gerais (UFMG), Belo Horizonte, Brazil; Department of Pediatrics, Interdisciplinary Laboratory of Medical Investigation, Faculty of Medicine, Unity of Pediatric Nephrology, Federal University of Minas Gerais (UFMG), Belo Horizonte, Brazil.
Nephrology (Carlton). 2014 Nov;19(11):714-20. doi: 10.1111/nep.12308.
The angiotensin type 2 (AT2 ) receptor takes part in the process of ureteric bud during kidney development. Therefore, the gene encoding AT2 receptor, the AGTR2 gene located in the X chromosome, is a potential candidate for genetic association with Congenital Anomalies of the Kidney and Urinary Tract (CAKUT). This study aimed to investigate whether AGTR2 gene polymorphisms are associated with CAKUT in general or even with common phenotypes of CAKUT in a Brazilian sample of paediatric patients.
We analyzed 290 paediatric patients with CAKUT and 262 healthy controls from the same geographic area. TaqMan single-nucleotide polymorphism (SNP) genotyping assays for AGTR2 gene at rs1403543, rs3736556, rs35474657, rs5193 and rs5194 were performed. The sample was in Hardy-Weinberg Equilibrium for all five SNPs.
The presence of CAKUT in general was not significantly associated with the SNPs included in this study. However, when patients were segregated according to major phenotypes, the diagnosis of Ureteropelvic Junction Obstruction (UPJO) was significantly associated with AGTR2 gene polymorphisms at rs3736556 and at rs5194. On the other hand, the diagnoses of vesicoureteral reflux and of multicystic dysplastic kidney were not associated with AGTR2 gene polymorphisms.
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.
血管紧张素2型（AT2）受体参与肾脏发育过程中的输尿管芽形成过程。因此，编码AT2受体的基因，即位于X染色体上的AGTR2基因，是与先天性肾脏和尿路畸形（CAKUT）存在遗传关联的潜在候选基因。本研究旨在调查AGTR2基因多态性是否与巴西儿科患者样本中的CAKUT总体相关，甚至与CAKUT的常见表型相关。
我们分析了290例患有CAKUT的儿科患者和来自同一地理区域的262例健康对照。对AGTR2基因的rs1403543、rs3736556、rs35474657、rs5193和rs5194进行了TaqMan单核苷酸多态性（SNP）基因分型检测。所有五个SNP的样本均处于哈迪-温伯格平衡状态。
总体上CAKUT的存在与本研究中包含的SNP无显著关联。然而，当根据主要表型对患者进行分类时，输尿管肾盂连接部梗阻（UPJO）的诊断与rs3736556和rs5194处的AGTR2基因多态性显著相关。另一方面，膀胱输尿管反流和多囊性发育不良肾的诊断与AGTR2基因多态性无关。
我们的结果支持AGTR2基因可能参与UPJO的发病机制，并且CAKUT的遗传起源可能因表型表达而异。
