PURPOSE: The renin-angiotensin system has an important role in the development of the kidney and ureter. It has been reported that disruption of the angiotensin II type 2 receptor (AT2) gene leads to congenital anomalies of the kidney and ureter in mice, including vesicoureteral reflux. In humans a single base A to G transition at position -1332 in intron 1 (A-1332G) of the AT2 gene has been reported to occur significantly more often in patients with ureteropelvic junction obstruction and primary obstructive megaureter than in controls. We investigate the incidence of A-1332G transition in patients with primary familial vesicoureteral reflux to determine if AT2 gene is involved in pathogenesis of this disease. MATERIALS AND METHODS: We evaluated the incidence of A-1332G transition in 82 male and 110 female patients, 111 male and 124 female nonaffected family members from 88 families in which 2 or more members had primary vesicoureteral reflux, and 106 male and 107 female controls with no unselected for reflux status. Genomic DNA was extracted from whole blood samples. Polymerase chain reaction method modified for fluorescent detection was used to type all samples for the A-1332G variant. Furthermore, to identify mutations in the coding sequence of the AT2 gene, we selected 61 patients from different families as well as 15 controls with no vesicoureteral reflux status. RESULTS: The incidence of A-1332G transition in male patients with primary familial vesicoureteral reflux and controls was 33% (27 of 82 patients) and 38% (41 of 106 controls), respectively, and, the incidence of A-1332G substituted allele in female patients and controls was 47% (104 of 220 total alleles) and 50% (107 of 214 total alleles), respectively. Moreover, the transmission/disequilibrium test revealed no significant skewing of genotype transmission from mother to children. None of the 61 patients or 15 controls carried by mutations or polymorphisms in the coding sequence of the AT2 gene. CONCLUSIONS: Although the AT2 gene has been reported to have a role in developmental anomalies of the kidney and ureter, our data indicate that it is not involved in the pathogenesis of primary familial vesicoureteral reflux.
PURPOSE: The renin-angiotensin system has an important role in the development of the kidney and ureter. It has been reported that disruption of the angiotensin II type 2 receptor (AT2) gene leads to congenital anomalies of the kidney and ureter in mice, including vesicoureteral reflux. In humans a single base A to G transition at position -1332 in intron 1 (A-1332G) of the AT2 gene has been reported to occur significantly more often in patients with ureteropelvic junction obstruction and primary obstructive megaureter than in controls. We investigate the incidence of A-1332G transition in patients with primary familial vesicoureteral reflux to determine if AT2 gene is involved in pathogenesis of this disease. MATERIALS AND METHODS: We evaluated the incidence of A-1332G transition in 82 male and 110 female patients, 111 male and 124 female nonaffected family members from 88 families in which 2 or more members had primary vesicoureteral reflux, and 106 male and 107 female controls with no unselected for reflux status. Genomic DNA was extracted from whole blood samples. Polymerase chain reaction method modified for fluorescent detection was used to type all samples for the A-1332G variant. Furthermore, to identify mutations in the coding sequence of the AT2 gene, we selected 61 patients from different families as well as 15 controls with no vesicoureteral reflux status. RESULTS: The incidence of A-1332G transition in male patients with primary familial vesicoureteral reflux and controls was 33% (27 of 82 patients) and 38% (41 of 106 controls), respectively, and, the incidence of A-1332G substituted allele in female patients and controls was 47% (104 of 220 total alleles) and 50% (107 of 214 total alleles), respectively. Moreover, the transmission/disequilibrium test revealed no significant skewing of genotype transmission from mother to children. None of the 61 patients or 15 controls carried by mutations or polymorphisms in the coding sequence of the AT2 gene. CONCLUSIONS: Although the AT2 gene has been reported to have a role in developmental anomalies of the kidney and ureter, our data indicate that it is not involved in the pathogenesis of primary familial vesicoureteral reflux.
Authors: H Kelly; C M Molony; J M Darlow; M E Pirker; A Yoneda; A J Green; P Puri; D E Barton Journal: J Med Genet Date: 2007-07-27 Impact factor: 6.318
Authors: Xiang-Tian Kong; Fang-Ming Deng; Ping Hu; Feng-Xia Liang; Ge Zhou; Anna B Auerbach; Nancy Genieser; Peter K Nelson; Edith S Robbins; Ellen Shapiro; Bechara Kachar; Tung-Tien Sun Journal: J Cell Biol Date: 2004-12-20 Impact factor: 10.539
Authors: Heather J Cordell; Rebecca Darlay; Pimphen Charoen; Aisling Stewart; Ambrose M Gullett; Heather J Lambert; Sue Malcolm; Sally A Feather; Timothy H J Goodship; Adrian S Woolf; Rajko B Kenda; Judith A Goodship Journal: J Am Soc Nephrol Date: 2009-12-03 Impact factor: 10.121