Related Experiment Videos
Angiotensin-converting enzyme gene insertion/deletion polymorphism and renal damage in childhood uropathies
A al-Eisa1, M Z Haider, B S Srivastva
1Pediatrics Department, Faculty of Medicine, Kuwait University, Kuwait.
Insights
The D allele of the angiotensin-converting enzyme (ACE) gene insertion/deletion polymorphism is associated with congenital urological abnormalities and renal parenchymal damage in Kuwaiti children. This finding may help understand disease heterogeneity.
Area of Science:
- Genetics
- Pediatric Nephrology
- Urology
Background:
- Congenital urological abnormalities are a significant cause of pediatric renal failure.
- The renin-angiotensin system plays a role in renal disorders.
- Genetic factors influencing the renin-angiotensin system may contribute to variable renal damage.
Purpose of the Study:
- To investigate the association between the angiotensin-converting enzyme (ACE) gene insertion/deletion polymorphism and congenital urological abnormalities in Kuwaiti children.
- To explore the relationship between ACE genotypes and renal parenchymal damage in this population.
Main Methods:
- Genomic DNA was extracted from blood samples of 47 children with urological abnormalities and 48 healthy controls.
- Angiotensin-converting enzyme (ACE) gene genotypes (ID polymorphism) were determined using polymerase chain reaction (PCR).
Main Results:
- The D allele of the ACE gene was more prevalent in children with urological abnormalities (87%) compared to controls.
- A higher incidence of renal parenchymal damage was observed in uropathy cases with the DD genotype (62%) compared to ID (26%) and II (12%) genotypes.
- The II genotype was significantly more frequent in controls (2%) than in cases (13%), while the ID genotype was less frequent in cases (29%) than in controls (46%).
Conclusions:
- The D allele of the ACE gene insertion/deletion polymorphism is associated with congenital urological abnormalities leading to renal parenchymal damage in Kuwaiti Arab children.
- This genetic polymorphism may contribute to the heterogeneity observed in renal damage among children with urological conditions.
Background:
The activation of the renin-angiotensin system in various renal disorders is well established. Congenital urological abnormalities, such as obstruction and reflux, are common causes of renal failure in children contributing to approximately 25% of chronic renal failure in this age group. While the outlook relates to the severity of initial renal damage, there is considerable heterogeneity in renal parenchymal destruction among individuals and the reasons for this heterogeneity are not fully understood. A polymorphism within intron 16 of the angiostensin-converting enzyme (ACE) gene has been shown to influence the activity of the renin-angiotensin system, thus, it may also have an impact on the expression of renal disorders. We have determined the incidence of this ID polymorphism of the ACE gene in 47 Kuwaiti children with different urological abnormalities leading to variable degrees of renal impairment and in 48 healthy control subjects with a similar ethnic background.
Methods:
Blood samples were collected from the patients (n = 47) and controls (n = 48), total genomic DNA extracted and the ACE genotypes were determined using a polymerase chain reaction-based method.
Results:
The DD genotype was detected in 27/47 (57%) cases compared with 25/48 (52%) controls (P = 0.439). The heterozygous genotype ID was found in 14/47 (29%) cases compared with 22/48 (46%) controls (P = 0.0138). The homozygous II genotype was detected in 6/47 (13%) cases compared with 1/48 (2%) controls (P = 0.0247). The D allele of ACE gene was detected in 41/47 (87%) uropathy cases when individuals with homozygous DD and heterozygous ID genotypes were considered collectively. The incidence of parenchymal damage was considerably higher in uropathy cases with DD genotype (62%) compared with those having ID (26%) and II (12%) genotypes.
Conclusions:
Our data suggest an association of D allele of the ACE gene insertion/deletion polymorphism and congenital urological abnormalities, which result in parenchymal damage in Kuwaiti Arab children.