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Mona S Habieb,1 Ashraf A Dawood,1 Mahmoud M Emara,2 Mohammad G Elhelbawy,3 Nesreen G Elhelbawy1 1Medical Biochemistry & Molecular Biology Department, Faculty of Medicine, Menoufia University, Shebin Elkom City, Egypt; 2Internal Medicine Department, Faculty of Medicine, Menoufia University, Shebin Elkom City, Egypt; 3Clinical Pathology Department, Faculty of Medicine, Menoufia University, Shebin Elkom City, EgyptCorrespondence: Nesreen G ElhelbawyMedical Biochemistry and Molecular Biology Department, Faculty of Medicine, Menoufia University, Shebin Elkom City 32511, EgyptTel +201069590533Fax +20482181009Email nesrin.elhelbawy@yahoo.comBackground: 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.Keywords: diabetic nephropathy, CYP2J2, EPHX2, real time PCR