Angiotensin II, type 2 receptor in the development of vesico‐ureteric reflux

Hohenfellner, Katharina; Hunley, Tracy E.; Yerkes, Elizabeth B.; Habermehl, Pirmin; Hohenfellner, R.; Kon, Valentina

doi:10.1046/j.1464-410x.1999.00923.x

Cited by 38 publications

(23 citation statements)

References 28 publications

(39 reference statements)

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“…The authors also observed suggestive linkage at 10q26 and 6q27. Our data implicate new VUR disease loci but do not confirm those mentioned previously except for chromosome 13. This provides further evidence of marked genetic heterogeneity associated with VUR.…”

Section: Discussioncontrasting

confidence: 79%

“…Reflux has been found to be associated with several loci in the HLA antigen complex. [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.…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Discussioncontrasting

confidence: 79%

Section: Introductionmentioning

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 discrepancy among these studies is more likely to be the result of the limited number of included patients because the genetic background, at least among Caucasians, does not differ. 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.…”

supporting

confidence: 91%

“…AT2R GENE AND CONGENITAL UROPATHIES population (57%) compared with other Caucasian (38%-42%) (7,9,16,18) and Japanese (30%) (10) controls. In Table 5, previous studies considering the A-1332G transition in patients with CAKUT are summarized.…”

mentioning

confidence: 99%

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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“…Yim et al 36 reported association between an AGTR2 intronic variant and diverse kidney malformations, although this was not replicated in two studies. 37,38 Yang et al 39 presented data for association with between a RET polymorphism (p.Gly691Ser) and VUR, but this was not replicated in an Irish cohort. 40 Jiang et al 41 reported a weak association between a UPK3A missense polymorphism and VUR.…”

Section: Discussionmentioning

confidence: 97%

Whole-Genome Linkage and Association Scan in Primary, Nonsyndromic Vesicoureteric Reflux

Cordell¹,

Darlay²,

Charoen

et al. 2010

Journal of the American Society of Nephrology

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Primary vesicoureteric reflux accounts for approximately 10% of kidney failure requiring dialysis or transplantation, and sibling studies suggest a large genetic component. Here, we report a wholegenome linkage and association scan in primary, nonsyndromic vesicoureteric reflux and reflux nephropathy. We used linkage and family-based association approaches to analyze 320 white families (661 affected individuals, generally from families with two affected siblings) from two populations (United Kingdom and Slovenian). We found modest evidence of linkage but no clear overlap with previous studies. We tested for but did not detect association with six candidate genes (AGTR2, HNF1B, PAX2, RET, ROBO2, and UPK3A). Family-based analysis detected associations with one single-nucleotide polymorphism (SNP) in the UK families, with three SNPs in the Slovenian families, and with three SNPs in the combined families. A case-control analysis detected associations with three additional SNPs. The results of this study, which is the largest to date investigating the genetics of reflux, suggest that major loci may not exist for this common renal tract malformation within European populations.

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Angiotensin II, type 2 receptor in the development of vesico‐ureteric reflux

Cited by 38 publications

References 28 publications

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

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

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

Whole-Genome Linkage and Association Scan in Primary, Nonsyndromic Vesicoureteric Reflux

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