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 environmental risk factors for CKD, such as HBP and hyperglycemia have been suggested; however, their interactions 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) using two pairs primers for rs35652124 and rs6721961 and by real-time PCR for rs2364723. Logistic regression analyses, adjusted for confounding factors and correction for multiple tests were performed. Results: Significant associations between decreased risk for presenting with CKD and the rs35652124 (A allele) and the rs2364723 (G allele) variants were detected. Other variables consistently associated with these alleles were HBP, BMI, 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 deceased risk for CKD in T2DM patients. Conclusion: This study showed for the first time that NFE2L2 variants are associated with decreased risk for CKD in the presence of environmental/metabolic risk factors related to kidney damage, including HBP, hyperuricemia and albuminuria in Mexican patients with diabetes.

Interactions Between Diet Quality and Interleukin-6 Genotypes Are Associated With Metabolic and Renal Function Parameters in Mexican Patients With Type 2 Diabetes Mellitus.

OBJECTIVE: The aim of this study was to evaluate the interaction between diet quality and interleukin (IL)-6 genotypes and its association with metabolic and renal function parameters in Mexican patients with type 2 diabetes mellitus (T2DM). DESIGN AND METHODS: Using an analytical cross-sectional design, 219 patients with T2DM (92 men; age 62 ± 10 years) were evaluated for selected metabolic and renal function parameters. Diet quality according to the Healthy Eating Index was evaluated and classified as good diet or poor diet in all patients. IL-6 serum concentrations and genotypes and haplotypes for IL6-597G > A (rs180097), -572G > C (rs180096), and -174G > C (rs180095) polymorphisms were determined. RESULTS: Eighty-two percent of patients reported having a poor diet. Carriers of alleles -572C and -174C showed higher high-density lipoprotein cholesterol levels (44 ± 12 vs. 40 ± 9 mg/dL; P = .01) and lower total cholesterol levels (184 ± 33 vs. 197 ± 42 mg/dL; P = .03) than did those homozygous for G/G. Neither IL6 genotypes nor haplotypes were significantly associated with serum concentrations of IL-6. Some significant interactions between IL6 genotypes/haplotypes and diet quality were associated with body mass index, waist circumference, high-density lipoprotein cholesterol levels, and estimated glomerular filtration rate. CONCLUSIONS: Interactions between diet quality and IL6 genotypes/haplotypes were associated with the main metabolic and renal function parameters in Mexican patients with T2DM. It will be important to consider genetic profiles in designing dietary portfolios and nutritional interventions for the management of such patients.