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

Autor(es)

Monteiro, M. B. ^[1] ; Patente, T. A. ^{[2, 1]} ; Mohammedi, K. ^{[2, 3]} ; Queiroz, M. S. ^[4] ; Azevedo, M. J. ^[5] ; Canani, L. H. ^[5] ; Parisi, M. C. ^[6] ; Marre, M. ^{[2, 3, 7]} ; Velho, G. ^[2] ; Correa-Giannella, M. L. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Fac Med, Lab Endocrinol Celular Mol LIM 25, BR-01246903 Sao Carlos, SP - Brazil

^[2] INSERM, Res Unit 695, Paris - France

^[3] Hop Xavier Bichat, AP HP, Dept Endocrinol Diabetol & Nutr, Paris - France

^[4] Univ Sao Paulo, Hosp & Clin, Fac Med, Div Endocrinol, Sao Paulo, SP - Brazil

^[5] Univ Fed Rio Grande do Sul, Hosp Clin Porto Alegre, Div Endocrinol, Porto Alegre, RS - Brazil

^[6] Univ Estadual Campinas UNICAMP, Fac Med, Dept Clin Med, Div Endocrinol, Campinas, SP - Brazil

^[7] Univ Paris Diderot, UFR Med, Paris - France

• Tipo de documento: Artigo Científico
• Fonte: Free Radical Research; v. 47, n. 10, p. 804-810, OCT 2013.
• Citações Web of Science: 7

Resumo

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. (AU)

• Processo FAPESP: 11/15015-8 - Associação entre Polimorfismos em Genes que Codificam Proteínas Pró- e Antioxidantes e a Susceptibilidade à Nefropatia em Coortes Francesas de Portadores de Diabetes Tipo 1: Validação de Resultados Observados em uma Casuística Brasileira.
• Beneficiário: Thiago Andrade Patente
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 09/09276-3 - Estudo de Polimorfismos em Genes que Codificam Enzimas Antioxidantes e Transportadores de Glicose e sua Associação com a Susceptibilidade a Complicações Crônicas em Pacientes Diabéticos Tipo 1
• Beneficiário: Maria Lucia Cardillo Corrêa Giannella
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 09/04162-0 - Estudo da Associação entre Polimorfismos em Genes Relacionados a Vias Antioxidantes Endógenas e a Susceptibilidade a Nefropatia em Pacientes Diabéticos Tipo 1
• Beneficiário: Maria Beatriz Camargo Monteiro Caillaud
• Modalidade de apoio: Bolsas no Brasil - Mestrado