Association of Variants of the NFE2L2 Gene with Metabolic and Kidney Function Parameters in Patients with Diabetes And/or Hypertension.

Background: Type 2 diabetes mellitus (T2DM) and high blood pressure (HBP) are the main risk factors for chronic kidney disease (CKD). Relationships between variants within the NFE2L2 gene and the presence of risk factors for CKD, such as HBP and hyperglycemia, have been suggested; however, their role on kidney parameters remains unclear.Aim: To analyze the association of NFE2L2 variants with metabolic and kidney parameters.Materials and Methods: Six-hundred and fifty-one patients grouped according to the diagnosis of T2DM (n = 166), T2DM+HBP (n = 348), and HBP (n = 137) were included. Metabolic characteristics were evaluated to identify risk factors and presence of CKD. Genotyping was performed by polymerase chain reaction (PCR) coupled to confronting two pair primers for rs35652124 and rs6721961 and by real-time PCR for rs2364723. Logistic regression analyses, adjusted by confounding factors and correction for multiple tests, were performed.Results: Significant associations of rs35652124 (allele A) and rs2364723 (allele G) variants with low risk for presenting CKD were detected. Other variables consistently associated with these alleles were HBP, body mass index, waist circumference, uric acid, and triglycerides. Haplotypes AAC and GCG (loci order: rs35652124-rs6721961-rs2364723) showed similar trends. After adjustment for age and sex and correction for multiple tests, only rs35652124 (odds ratio [OR] = 0.5; confidence interval at 95% (CI95%), 0.3-0.9; p = 0.04) and rs2364723 (OR = 0.3; CI95%, 0.1-0.8; p = 0.009) variants remained associated with low risk for CKD in T2DM patients.Conclusion: This study showed for the first time that NFE2L2 variants were associated with low risk for CKD and with some traits related to kidney damage, such as HBP, hyperuricemia, and albuminuria, in Mexican patients with diabetes.