The objective of this study was to investigate whether mutations of the renin-angiotensin system genes are involved in primary vesicoureteric reflux (VUR) and VUR-associated renal scarring. The M235T polymorphism of the angiotensinogen (ATG) gene, the I/D polymorphism of the angiotensin converting enzyme (ACE) gene, and the A1166C polymorphism of the angiotensin II grade 1 receptor (AT1) gene were identified in 77 patients with primary VUR (aged 6.9±3.2 years, mean±SD) and 80 healthy controls (aged 33±7 years). Thirty-eight of the 77 VUR patients had high-grade VUR (grade I-III) and 39 had high-grade VUR (grade IV and V). Renal scarring was found in 43 VUR patients, while 34 patients had normal kidneys on dinercaptosuccinic acid scan. The ACE gene polymorphism has determined by polymerase chain reaction and the ATG and AT1 gene polymorphisms were determined by single-step LightCycler technology. We found significant over-representation of the DD genotype in patients with renal scarring (44%) compared with normal controls (23%, P<0.05) and patients with no scar formation (21%, P<0.05). Significantly higher D and significantly lower I allele frequencies were present in VUR patients with scarred kidneys (D allele 0.64 and I allele 0.36) compared with controls (D allele 0.53 and I allele 0.47, P<0.05) and patients with unscarred kidneys (D allele 0.4 and I allele 0.6, P<0.05). No differences in the ATG and AT1 genotype distributions and allele frequencies were observed in VUR patients compared with the normal population. The DD genotype and D allele of ACE may be a genetic susceptibility factor contributing to scar formation in VUR. We detected no linkage of genetic polymorphisms of ATG and AT1 to VUR and VUR-associated renal scarring.
- Angiotensin II type 1 receptor
- Angiotensin converting ezyme
- LightCycler technology
- Renal scarring
- Vesicoureteric reflux