MARIA BEATRIZ CAMARGO MONTEIRO CAILLAUD

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LIM/18 - Laboratório de Carboidratos e Radioimunoensaios, Hospital das Clínicas, Faculdade de Medicina

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  • article 18 Citação(ões) na Scopus
    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
    (2013) MONTEIRO, M. B.; PATENTE, T. A.; MOHAMMEDI, K.; QUEIROZ, M. S.; AZEVEDO, M. J.; CANANI, L. H.; PARISI, M. C.; MARRE, M.; VELHO, G.; CORREA-GIANNELLA, M. L.
    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.
  • article 23 Citação(ões) na Scopus
    Thioredoxin interacting protein expression in the urinary sediment associates with renal function decline in type 1 diabetes
    (2016) MONTEIRO, Maria Beatriz; SANTOS-BEZERRA, Daniele Pereira; THIEME, Karina; ADMONI, Sharon Nina; PEREZ, Ricardo Vessoni; MACHADO, Cleide Guimaraes; QUEIROZ, Marcia Silva; NERY, Marcia; OLIVEIRA-SOUZA, Maria; WORONIK, Viktoria; PASSARELLI, Marisa; GIANNELLA-NETO, Daniel; MACHADO, Ubiratan Fabres; CORREA-GIANNELLA, Maria Lucia
    Aims: Thioredoxin interacting protein (TXNIP), an inhibitor of antioxidant thioredoxin (Trx), is upregulated by hyperglycemia and implicated in pathogenesis of diabetes complications. We evaluated mRNA expressions of genes encoding TXNIP and Trx (TXN) in urinary sediment and peripheral blood mononuclear cells (PBMC) of type 1 diabetes (T1D) patients with different degrees of chronic complications. Methods: qPCR was employed to quantify target genes in urinary sediment (n=55) and PBMC (n=161) from patients sorted by presence or absence of diabetic nephropathy (DN), retinopathy, peripheral and cardiovascular neuropathy; 26 healthy controls and 13 patients presenting non-diabetic nephropathy (focal and segmental glomerulosclerosis, FSGS) were also included. Results: Regarding the urinary sediment, TXNIP (but not TXN) expression was higher in T1D (p=0.0023) and FSGS (p=0.0027) patients versus controls. Expressions of TXNIP and TXN were higher, respectively, in T1D patients with versus without DN (p=0.032) and in those with estimated glomerular filtration rate (eGFR) <60 versus >= 60 mL/min/1.73 m(2) (p=0.008). eGFR negatively correlated with TXNIP (p=0.04, r=-0.28) and TXN (p=0.04, r=-0.30) expressions. T1D patients who lost >= 5 mL/min/1.73 m(2) yearly of eGFR presented higher basal TXNIP expression than those who lost<5 mL/min/1.73 m(2) yearly after median follow-up of 24 months. TXNIP (p<0.0001) and TXN (p=0.002) expressions in PBMC of T1D patients were significantly higher than in controls but no differences were observed between patients with or without chronic complications. Conclusions: TXNIP and TXN are upregulated in urinary sediment of T1D patients with diabetic kidney disease (DKD), but only TXNIP expression is associated with magnitude of eGFR decline.