Genetic Polymorphism of the Renin-Angiotensin System on the Development of Primary Vesicoureteral Reflux

Yim, Hyung Eun; Jung, Min Ji; Choi, Byung Min; Bae, In Sun; Yoo, Kee Hwan; Hong, Young Sook; Lee, Joo Won; Kim, Soon Kyum

doi:10.1159/000076620

Cited by 18 publications

(19 citation statements)

References 24 publications

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“…The present study showed no significant difference in the frequency of the A-1332G transition between patients with VUR and controls, consistent with previous studies in Caucasian and Japanese patients (10,11,16,18). In contrast, Yim et al (17) found that this transition occurred significantly less often in Korean patients (males and females) with VUR than in normal controls. Previous studies (9,11), including ours, showed no significant difference in the frequency of the A-G transition in patients with PUV, which is expected because the At2r mRNA expression is absent in the urethral area (7).…”

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confidence: 92%

Angiotensin II Type 2 Receptor Gene Polymorphism in Caucasian Children With a Wide Spectrum of Congenital Anomalies of the Kidney and Urinary Tract

et al. 2007

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ABSTRACT:The A-1332G transition of the angiotensin II type 2 receptor (AT2R) gene was found to occur more often in males with ureteropelvic (UPJO) or ureterovesical junction obstruction (UVJO). However, other studies have shown controversial results. ⌻he frequency of this polymorphism was investigated in 275 Caucasian children (153 boys, 122 girls) with a wide spectrum of congenital anomalies both of upper (165) and lower (110) urinary tract system and in 200 controls (100 boys, 100 girls). Among the included malformations, renal agenesis and duplex collecting system (DCS) were studied for the first time. The frequency of the G allele did not differ among patients (193 of 397 total alleles, 48.6%) and controls (146 of 300, 48.7%). No significant difference was also found in the frequency of the G allele in subgroups of congenital uropathies compared with controls. When analysis was performed in males and females separately, no significant difference was found in the frequency of the G allele in male (45.1%) or female (50.8%) patients compared with male (57.0%) or female (44.5%) controls. Our data indicate that the AT2R gene A-1332G transition is not associated with the development of human congenital uropathies and further investigations should be carried out to unravel their etiology. C ongenital anomalies of the kidney and urinary tract (CAKUT) account for up to 30% of all anomalies diagnosed prenatally and constitute the main cause of chronic renal failure in infants and young children. Although the etiology of most of these anomalies has not been identified, experimental studies have identified several genes that are implicated in nephrogenesis and in which the derangement result in renal maldevelopment (1,2).In recent years, published data have shown that the reninangiotensin system, besides its role in maintaining blood pressure as well as fluid and electrolytes homeostasis, has an important role in kidney development (3). AT2R is abundantly expressed in fetal tissues (4) and decreases rapidly after birth (5). It has been shown to mediate programmed cell death, playing an important role in developmental biology and pathophysiology (4). The expression of the AT2R is higher and localized to the mesenchyme at the time of the ureteric bud branching (3). The gene encoding AT2R is located on the X chromosome, so that normal males carry only one copy, whereas normal females carry two copies. It consists of three exons and two introns, with the entire coding region located on exon 3 (6).Experimental studies have shown that the establishment of CAKUT is preceded by delayed apoptosis of the undifferentiated mesenchymal cells that initially occupy the metanephros and densely surround the wolffian duct and ureter (7). This abnormal apoptosis hinders the normal interaction between the ureteric bud and metanephric blastema, resulting in CAKUT (8). Moreover, At2r gene null mutant mice display CAKUT, which mimics human CAKUT (7).Studies on the human AT2R gene identified a polymorphic locus in a large proportion of the gen...

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Angiotensin II Type 2 Receptor Gene Polymorphism in Caucasian Children With a Wide Spectrum of Congenital Anomalies of the Kidney and Urinary Tract

et al. 2007

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“…[7][8][9] Several groups have sought to identify associations with VUR and various candidate genes, including PAX-2, 10,11 G proteins, 12 angiotensin II, type 2 receptor 13 and components of the renin-angiotensin system. [14][15][16][17] Unfortunately, none of these have been proven to be reliable markers of the reflux trait. There is a lack of replication of previously reported linkages.…”

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confidence: 99%

A genome scan in affected sib-pairs with familial vesicoureteral reflux identifies a locus on chromosome 5

et al. 2009

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The basis for vesicoureteral reflux (VUR) is considered to be primarily genetic, with a 30-50% incidence of VUR in first-degree relatives of patients. The search for the causative gene or genes has been elusive, likely because of VUR being genetically heterogeneous with complex inheritance patterns. In this study, a genome-wide analysis of VUR with high-density single nucleotide polymorphisms was conducted with the aim of identifying susceptibility loci for VUR in 98 families with two or more affected children. Using the affected sib-pair method of analysis in 150 sib-pairs, we identified a genome-wide statistically significant linkage peak with an LOD score greater than 4 on chromosome 5 and two linkage peaks with LOD scores greater than 3.6 on chromosomes 13 and 18 were identified in these 98 families. These results suggested that multiple genes are likely to contribute to the formation of VUR phenotype. Further mapping of these linkage peaks may help identify the causative genes.

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“…Many in vitro studies have shown that the expression of individual cytokines or cytokine receptors is influenced by polymorphic genotypes within regulatory regions, and that these polymorphic genotypes may play pivotal roles in the pathogenesis and progression of chronic renal diseases (4). We also recently reported the associations of genetic polymorphisms of the reninangiotensin system, which are known to affect renal pathophysiology and primary VUR (5).…”

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Genetic Control of VEGF and TGF-β1 Gene Polymorphisms in Childhood Urinary Tract Infection and Vesicoureteral Reflux

et al. 2007

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ABSTRACT:We investigated whether genetic polymorphisms of vascular endothelial growth factor (VEGF) and transforming growth factor-␤1 (TGF-␤1), potential candidate genes in the pathogenesis of urinary tract infection (UTI) and vesicoureteral reflux (VUR), are associated with the susceptibility to UTI and VUR, and renal scarring. We recruited 89 controls and 86 UTI and 58 VUR children. The UTI group was subdivided into two groups according to renal scarring. Two polymorphisms of VEGF and three of TGF-␤1 genes were investigated by using PCR-restriction fragment length polymorphism analysis. In both UTI and VUR groups, there was an increase in frequency of the VEGF -460 CC (control, 4.3; UTI, 15.9; VUR, 17.8%; p Ͻ 0.05), TGF-␤1 -509 CC (control, 8.7; UTI, 34.6; VUR, 35.1%; p Ͻ 0.001), and TGF-␤1 -800 GG genotypes (control, 19.1; UTI, 40.5; VUR, 40.4%; p Ͻ 0.05). An increase in the TGF-␤1 ϩ869 CC (scar-positive, 35.4; scar-negative, 10.3%; p Ͻ 0.05) and a decrease in the ϩ869 TC genotype (scar-positive, 29.2; scarnegative, 55.2%; p Ͻ 0.05) were observed in the scar-positive subjects. There were no differences in ϩ405 VEGF genotype frequencies. The VEGF T-460C and the TGF-␤1 C-509T, G-800A, and T869C polymorphisms could be genetic markers of the process of UTI and VUR. (Pediatr Res 62: 183-187, 2007)

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Genetic Polymorphism of the Renin-Angiotensin System on the Development of Primary Vesicoureteral Reflux

Cited by 18 publications

References 24 publications

Angiotensin II Type 2 Receptor Gene Polymorphism in Caucasian Children With a Wide Spectrum of Congenital Anomalies of the Kidney and Urinary Tract

Angiotensin II Type 2 Receptor Gene Polymorphism in Caucasian Children With a Wide Spectrum of Congenital Anomalies of the Kidney and Urinary Tract

A genome scan in affected sib-pairs with familial vesicoureteral reflux identifies a locus on chromosome 5

Genetic Control of VEGF and TGF-β1 Gene Polymorphisms in Childhood Urinary Tract Infection and Vesicoureteral Reflux

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