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Early Evidence on Genetic Polymorphisms in Conferring A "Two-Hit" Propensity to Renal Injury in Asian Indian Children
Suramya Anand1, Minu Bajpai1, Alok Kumar1
1Department of Paediatric Surgery, AIIMS, New Delhi, India.
Background:
Congenital anomalies of the kidney and urinary tract (CAKUT) are a common cause of end-stage renal disease in children. While certain nephrogenic genes have been incriminated in these malformations, data to identify the frequency of gene polymorphisms in Asian Indian children with CAKUT are scarce. This study was done to identify the effect of polymorphisms in paired-box gene 2 (PAX2), bone morphogenetic protein (BMP)-4, angiotensin-converting enzyme (ACE), and angiotensin II receptor Type 2 (AGTR2) nephrogenic genes on the development of CAKUT.
Materials And Methods:
In this prospective cohort study, 158 children <12 years old (86 cases with CAKUT and 72 age-matched controls) were analyzed. DNA from both sets was extracted from peripheral blood using the Keygen DNA extraction kit, and single-nucleotide gene polymorphisms (SNPs) in PAX2, BMP-4, ACE, and AGTR2 nephrogenic genes were detected by polymerase chain reaction (PCR) using previously published primers and PCR conditions.
Results:
The presence of A allele SNP for AGTR2 gene at rs3736556 was found to be significantly correlated with the development of ureteropelvic junction obstruction and vesicoureteral reflux (VUR) with the TT allelic genotype having a lower incidence of pelviureteric junction obstruction (odds ratio [OR] 0.18 [95% confidence interval [CI], 0.06-0.55], P = 0.01) and VUR (OR 0.31 [95% CI, 0.11-0.91], P = 0.03). Furthermore, on substratification of the patients with the presence of the A allele of AGTR2, 24 out of 27 patients with scarring were found to harbor the D allele of the ACE gene, thus predisposing them to further renal damage.
Conclusion:
This study points to early evidence in the implication of nephrogenic genes in development as well as predisposition to renal injury in Asian Indian patients with CAKUT.
Insights
Gene variations in Asian Indian children with congenital anomalies of the kidney and urinary tract (CAKUT) were studied. The AGTR2 gene A allele correlated with ureteropelvic junction obstruction and VUR, suggesting a genetic predisposition to kidney disease.
Area of Science:
- Pediatric Nephrology
- Medical Genetics
- Urology
Background:
- Congenital anomalies of the kidney and urinary tract (CAKUT) are a leading cause of pediatric end-stage renal disease.
- Limited data exists on the frequency of gene polymorphisms in Asian Indian children with CAKUT.
- Nephrogenic genes are implicated in CAKUT, but their specific roles require further investigation.
Purpose of the Study:
- To investigate the association between polymorphisms in key nephrogenic genes and the development of CAKUT in Asian Indian children.
- To identify specific gene variants that may predispose children to CAKUT and subsequent renal damage.
Main Methods:
- A prospective cohort study involving 158 children under 12 years old (86 CAKUT cases, 72 controls).
- DNA extraction from peripheral blood followed by polymerase chain reaction (PCR) to detect single-nucleotide polymorphisms (SNPs) in PAX2, BMP-4, ACE, and AGTR2 genes.
- Analysis of allelic genotypes and their correlation with CAKUT development and complications.
Main Results:
- The A allele of the AGTR2 gene (rs3736556) showed a significant correlation with ureteropelvic junction obstruction and vesicoureteral reflux (VUR).
- The TT allelic genotype of AGTR2 was associated with a lower incidence of pelviureteric junction obstruction and VUR.
- Among patients with the AGTR2 A allele, the D allele of the ACE gene was frequently observed in those with renal scarring, indicating a predisposition to further kidney damage.
Conclusions:
- This study provides initial evidence linking specific nephrogenic genes to the development of CAKUT in Asian Indian children.
- Findings suggest that AGTR2 and ACE gene polymorphisms may play a role in both CAKUT pathogenesis and the progression of renal injury.
- Further research is warranted to elucidate the precise mechanisms and clinical implications of these genetic associations.
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