Catalase activity, allelic variations in the catalase gene and risk of kidney complications in patients with type 1 diabetes

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Mohammedi, Kamel ^{[1, 2]} ; Patente, Thiago A. ^{[1, 3]} ; Bellili-Munoz, Naiema ^[1] ; Driss, Fathi ^{[4, 5]} ; Monteiro, Maria Beatriz ^[3] ; Roussel, Ronan ^{[6, 2, 7]} ; Pavin, Elizabeth J. ^[8] ; Seta, Nathalie ^{[5, 9]} ; Fumeron, Frederic ^{[6, 1]} ; Azevedo, Mirela J. ^[10] ; Canani, Luis H. ^[10] ; Hadjadj, Samy ^{[11, 12, 13, 14]} ; Marre, Michel ^{[6, 1, 2]} ; Correa-Giannella, Maria Lucia ^[3] ; Velho, Gilberto ^[1]

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^[1] Inserm Res U695, F-75018 Paris - France

^[2] Hop Xavier Bichat, AP HP, Dept Diabetol Endocrinol & Nutr, Paris - France

^[3] Univ Sao Paulo, Fac Med, Lab Endocrinol Celular & Mol LIM 25, BR-09500900 Sao Paulo - Brazil

^[4] INSERM, Res Unit 773, Paris - France

^[5] Hop Xavier Bichat, AP HP, Dept Biochem, Paris - France

^[6] Univ Paris Diderot, UFR Med, Paris - France

^[7] INSERM, Res Unit 872, Paris - France

^[8] Univ Estadual Campinas, Fac Med, Dept Clin Med, Div Endocrinol, Campinas, SP - Brazil

^[9] Univ Paris Diderot, UFR Pharmacie, Paris - France

^[10] Univ Fed Rio Grande do Sul, Hosp Clin Porto Alegre, Div Endocrinol, Porto Alegre, RS - Brazil

^[11] Univ Poitiers, Ctr Hosp, Dept Endocrinol & Diabetol, Poitiers - France

^[12] INSERM, Res Unit 1082, Poitiers - France

^[13] INSERM, CIC 0802, Poitiers - France

^[14] Univ Poitiers, UFR Med & Pharmacie, Poitiers - France

• Tipo de documento: Artigo Científico
• Fonte: Diabetologia; v. 56, n. 12, p. 2733-2742, DEC 2013.
• Citações Web of Science: 6

Resumo

Oxidative stress is involved in the pathogenesis of diabetic nephropathy. The antioxidant enzyme catalase plays a key role in redox regulation in the kidney. We investigated associations of catalase gene (CAT) polymorphisms and plasma catalase activity with diabetic nephropathy in type 1 diabetic patients. We genotyped nine single nucleotide polymorphisms (SNPs) in the CAT region in participants from the Survival Genetic Nephropathy (SURGENE) (340 French participants, 10 year follow-up) and the G,n,tique de la N,phropathie Diab,tique (GENEDIAB) (444 Belgian and French participants, 8 year follow-up) study cohorts. Replication was performed in a Brazilian cross-sectional cohort (n = 451). Baseline plasma catalase activity was measured in SURGENE (n = 120) and GENEDIAB (n = 391) participants. The A allele of rs7947841 was associated with the prevalence of incipient (OR 2.79, 95% CI 1.21, 6.24, p = 0.01) and established or advanced nephropathy (OR 5.72, 95% CI 1.62, 22.03, p = 0.007), and with the incidence of renal events, which were defined as new cases of microalbuminuria or progression to a more severe stage of nephropathy during follow-up (HR 1.82, 95% CI 1.13, 2.81, p = 0.01) in SURGENE participants. The same risk allele was associated with incipient nephropathy (OR 3.13, 95% CI 1.42, 7.24, p = 0.004) and with the incidence of end-stage renal disease (ESRD) (HR 2.11, 95% CI 1.23, 3.60, p = 0.008) in GENEDIAB participants. In both cohorts, the risk allele was associated with lower catalase activity. Associations with incipient and established or advanced nephropathy were confirmed in the replication cohort. CAT variants were associated with the prevalence and incidence of diabetic nephropathy and ESRD in type 1 diabetic patients. Our results confirm the protective role of catalase against oxidative stress in the kidney. (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