Association of AGT and AGTR1 gene polymorphisms with chronic kidney disease: a case-control and in silico study.

BACKGROUND

Chronic kidney disease (CKD) is a complex disease influenced by genetic and environmental factors. Polymorphisms in RAAS genes have been implicated in kidney disease, though their influence on disease susceptibility varies across studies. The AGT and AGTR1 are key candidate genes of the RAAS cascade, essential for kidney function.

METHODS AND

RESULTS

This study investigated the association of AGT (rs699) and AGTR1 (rs5186) polymorphisms with susceptibility to CKD. A total of 380 participants were recruited in this hospital-based case-control study and genotyping was performed using PCR- RFLP method. Statistical analyses were conducted using SPSS Statistics version 26.0. Computational analysis was done to predict the pathogenicity of missense variant rs699 and its effect on structure and function of AGT; however, rs5186, a 3' UTR non-coding variant of the AGTR1 gene was excluded. Our findings showed that the AGT (rs699) T allele was more frequent in controls (46.9%) than in CKD cases (35.3%), suggesting a potential protective role against CKD (p = 0.001). No significant associations were observed in AGTR1 (rs5186) and CKD (p > 0.05). Furthermore, the studied polymorphisms did not significantly affect serum creatinine, urea, or eGFR levels in CKD patients. In silico analysis predicted the AGT rs699 variant to be likely benign, with slightly decreased AGT protein stability and binding affinity to renin.

CONCLUSIONS

The results suggest a significant association of the AGT (rs699) polymorphism with CKD. Computational findings support a limited functional impact of the rs699 variant. Further research, including functional studies and investigations in larger cohorts, is warranted to assess the potential of these polymorphisms as biomarkers for CKD risk.