The role of CYP4A11 and EPHX2 genetic polymorphisms in chronic kidney disease progression in hypertensive Egyptian patients

Background: Chronic kidney disease (CKD) is a global disease in which the kidney gradually loses its function. Hypertension has a direct effect on the appearance and development of CKD. Cytochrome P450 (CYP) and epoxide hydroxylase (EPHX2) participate in blood pressure regulation. Aim: We aimed to examine role of CYP4A11 and EPHX2 genetic polymorphisms in CKD progression in hypertensive CKD patients. Methods: In this case‒control study, we incorporated ninety-six hypertensive CKD patients, and ninety-six apparently healthy normotensive individuals were selected as controls. three tagging single nucleotide polymorphisms (tSNPs) in CYP4A11 and three in EPHX2 were selected in our study. We performed polymerase chain reaction (PCR) and then correlated the genotyping results with CKD risk. Results: Our study identified significant associations between CYP4A11 and EPHX2 polymorphisms and CKD risk in hypertensive Egyptian patients. The GC and CC genotypes of CYP4A11 rs3890011 (OR = 2.431, 2.536), also GA and AA genotypes of rs9332982 (OR = 2.464, 8.969) showed increased CKD risk. Similarly, the AG and GG genotypes of EPHX2 rs1042032 (OR = 2.115, 2.485), the AG and GG genotypes of EPHX2 rs41507953 (OR = 2.323, 4.425), the GA/AA genotypes of rs751141 (OR = 2.656, 4.869) were risk factors. The CYP4A11 GCG haplotype was protective (OR = 0.368), while CYP4A11 GCA and EPHX2 GGA (OR = 3.185, 3.111) showed increased risk. Conclusion: Genetic polymorphisms in CYP4A11 and EPHX2 are associated with CKD risk in hypertensive CKD patients. Specific genotypes and haplotypes may influence CKD progression, highlighting their potential as genetic markers for risk assessment.