Genetic association of ACE insertion/deletion and CYP11B2 -344T/C polymorphisms with susceptibility to chronic kidney disease: a case-control study

Chronic kidney disease (CKD) is influenced by genetic and environmental factors. ACE I/D and CYP11B2 polymorphism have been associated with kidney disease, though their impact varies across studies. This study aimed to investigate the association of the ACE I/D and CYP11B2 -344T/C polymorphisms with susceptibility to CKD.

This case-control study included 200 CKD patients and 180 control subjects. Genotyping for ACE I/D and CYP11B2 polymorphism was performed by the Polymerase Chain Reaction and RFLP method, and allele and genotype frequencies were analysed using the chi-square test. In silico analysis was conducted using the AliBaba2.1 tool to assess the effect of ACE I/D and CYP11B2 polymorphism on transcription factor binding to DNA target sequences.

No significant association was observed between the ACE DD genotype and CKD after adjustment for comorbidities, diet, and addiction [adjusted odds ratio (AOR) = 0.915, 95% confidence interval (CI) = 0.372–2.251, p = 0.847]. The CYP11B2 -344T/C CT genotype [AOR = 0.329, 95% CI = 0.148–0.732, p = 0.006] and dominant model (CT + CC) [AOR = 0.425, 95% CI = 0.211–0.854, p = 0.016] showed a significant association with CKD. Furthermore, ACE I/D but not CYP11B2 -344T/C polymorphism was significantly associated with variation in serum urea, creatinine, phosphorus, and eGFR levels in CKD patients (p < 0.05). In silico analysis predicted potential loss of transcription factor binding sites in the D allele of ACE I/D and the C allele of CYP11B2-344T/C.

The findings suggest that the CYP11B2 -344T/C but not the ACE I/D polymorphisms may modulate susceptibility to CKD. The in silico analysis predicted allele-specific transcription factor binding alterations, implying regulatory functional relevance, warranting functional validation.