The Human Genetic Variants CYP2J2 rs2280275 and EPHX2 rs751141 and Risk of Diabetic Nephropathy in Egyptian Type 2 Diabetic Patients.

Background: Diabetic nephropathy (DN), the primary driver of end-stage kidney disease, is a problem with serious consequences for society's health. Single nucleotide polymorphisms (SNPs) can define differences in susceptibility to DN and aid in development of personalized treatment. Giving the importance of epoxyeicosatrienoic acids (EETs) in kidney health, we aimed to study the association between two SNPs in the genes controlling synthesis and degradation of EETs (CYP2J2 rs2280275 and EPHX2 rs751141 respectively) and susceptibility of type 2 diabetes mellitus (T2DM) patients to develop DN.

Patients and methods: Two hundred subjects were enrolled and categorized into three groups: group I (80 T2DM patients with DN), group II (60 T2DM patients without DN) and group III (60 healthy controls). Urea, creatinine, albumin/creatinine ratio (ACR), and eGFR were measured for all participants. Genotyping of CYP2J2 rs2280275 and EPHX2 rs751141 was done by real time PCR.

Results: There was no significant difference between the studied groups regarding CYP2J2 rs2280275. In contrast, EPHX2 rs751141 was associated with increased risk of DN under a dominant model (GG vs GA+AA: OR=0.375; 95% CI (0.19-0.75), P=0.006) in unadjusted model and after adjustment for age and sex (OR=0.440; 95% CI (0.21-0.92), P=0.029), recessive model (AA vs GG+GA: OR=0.195; 95% CI (0.05-0.74), P=0.017) and additive model (GA vs GG+AA): OR=0.195; 95% CI (0.05-0.74), P=0.017).

Conclusion: CYP2J2 rs2280275 was not associated with DN predisposition. However, EPHX2 rs751141 could be a genetic marker for development and progression of DN among Egyptian T2DM patients.