Sex-specific associations of variants in regulatory regions of NADPH oxidase-2 (CYBB) and glutathione peroxidase 4 (GPX4) genes with kidney disease in type 1 diabetes.

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  • Additional Information
    • Source:
      Publisher: Informa Healthcare Country of Publication: England NLM ID: 9423872 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1029-2470 (Electronic) Linking ISSN: 10292470 NLM ISO Abbreviation: Free Radic Res Subsets: MEDLINE
    • Publication Information:
      Publication: London : Informa Healthcare
      Original Publication: Yverdon, Switzerland : New York, NY : Harwood Academic ; distributed by STBS Ltd., c1994-
    • Subject Terms:
      Diabetes Complications/*metabolism ; Diabetes Mellitus, Type 1/*enzymology ; Diabetes Mellitus, Type 1/*genetics ; Glutathione Peroxidase/*genetics ; Kidney Diseases/*enzymology ; Kidney Diseases/*genetics ; Membrane Glycoproteins/*genetics ; NADPH Oxidases/*genetics; Adult ; Diabetes Complications/genetics ; Female ; Genetic Predisposition to Disease ; Glutathione Peroxidase/metabolism ; Humans ; Male ; Membrane Glycoproteins/metabolism ; NADPH Oxidase 2 ; NADPH Oxidases/metabolism ; Oxidative Stress/genetics ; Phospholipid Hydroperoxide Glutathione Peroxidase ; Polymorphism, Single Nucleotide ; Risk Factors ; Sex Factors
    • Abstract:
      Oxidative stress is involved in the pathophysiology of diabetic nephropathy. The superoxide-generating nicotinamide adenine dinucleotide phosphate-oxidase 2 (NOX2, encoded by the CYBB gene) and the antioxidant enzyme glutathione peroxidase 4 (GPX4) play opposing roles in the balance of cellular redox status. In the present study, we investigated associations of single nucleotide polymorphisms (SNPs) in the regulatory regions of CYBB and GPX4 with kidney disease in patients with type 1 diabetes. Two functional SNPs, rs6610650 (CYBB promoter region, chromosome X) and rs713041 (GPX4 3'untranslated region, chromosome 19), were genotyped in 451 patients with type 1 diabetes from a Brazilian cohort (diabetic nephropathy: 44.6%) and in 945 French/Belgian patients with type 1 diabetes from Genesis and GENEDIAB cohorts (diabetic nephropathy: 62.3%). The minor A-allele of CYBB rs6610650 was associated with lower estimated glomerular filtration rate (eGFR) in Brazilian women, and with the prevalence of established/advanced nephropathy in French/Belgian women (odds ratio 1.75, 95% CI 1.11-2.78, p = 0.016). The minor T-allele of GPX4 rs713041 was inversely associated with the prevalence of established/advanced nephropathy in Brazilian men (odds ratio 0.30, 95% CI 0.13-0.68, p = 0.004), and associated with higher eGFR in French/Belgian men. In conclusion, these heterogeneous results suggest that neither CYBB nor GPX4 are major genetic determinants of diabetic nephropathy, but nevertheless, they could modulate in a gender-specific manner the risk for renal disease in patients with type 1 diabetes.
    • Accession Number:
      0 (Membrane Glycoproteins)
      EC 1.11.1.12 (Phospholipid Hydroperoxide Glutathione Peroxidase)
      EC 1.11.1.9 (Glutathione Peroxidase)
      EC 1.6.3.- (CYBB protein, human)
      EC 1.6.3.- (NADPH Oxidase 2)
      EC 1.6.3.- (NADPH Oxidases)
    • Publication Date:
      Date Created: 20130808 Date Completed: 20140520 Latest Revision: 20191210
    • Publication Date:
      20221213
    • Accession Number:
      10.3109/10715762.2013.828347
    • Accession Number:
      23919599