Kamel Mohammedi1, Thiago A Patente2, Naima Bellili-Muñoz3, Fathi Driss4, Hervé Le Nagard5, Frédéric Fumeron6, Ronan Roussel7, Samy Hadjadj8, Maria Lúcia Corrêa-Giannella9, Michel Marre7, Gilberto Velho10. 1. INSERM, UMRS 1138, Centre de Recherche des Cordeliers, 15 rue de l'École de Médecine, 75006, Paris, France; Assistance Publique Hôpitaux de Paris, Bichat Hospital, DHU FIRE, Department of Diabetology, Endocrinology and Nutrition, 46 rue Henri Huchard, 75018, Paris, France. 2. INSERM, UMRS 1138, Centre de Recherche des Cordeliers, 15 rue de l'École de Médecine, 75006, Paris, France; Laboratório de Endocrinologia Celular e Molecular (LIM-25), Faculdade de Medicina da Universidade de São Paulo (FMUSP), Avenida Dr. Arnaldo 455, CEP 01246903, São Paulo, SP, Brazil. 3. INSERM, UMRS 1138, Centre de Recherche des Cordeliers, 15 rue de l'École de Médecine, 75006, Paris, France. 4. INSERM, Research Unit 773, 16 rue Henri Huchard, 75018, Paris, France; Assistance Publique Hôpitaux de Paris, Bichat Hospital, Department of Biochemistry, 46 rue Henri Huchard, 75018, Paris, France. 5. INSERM, Research Unit 1137 - IAME, 16 rue Henri Huchard, 75018, Paris, France. 6. INSERM, UMRS 1138, Centre de Recherche des Cordeliers, 15 rue de l'École de Médecine, 75006, Paris, France; Université Paris Diderot, Sorbonne Paris Cité, UFR de Médecine, 16 rue Henri Huchard, 75018, Paris, France. 7. INSERM, UMRS 1138, Centre de Recherche des Cordeliers, 15 rue de l'École de Médecine, 75006, Paris, France; Assistance Publique Hôpitaux de Paris, Bichat Hospital, DHU FIRE, Department of Diabetology, Endocrinology and Nutrition, 46 rue Henri Huchard, 75018, Paris, France; Université Paris Diderot, Sorbonne Paris Cité, UFR de Médecine, 16 rue Henri Huchard, 75018, Paris, France. 8. Centre Hospitalier Universitaire de Poitiers, Department of Endocrinology and Diabetology, 2 rue de la Milétrie, 86021, Poitiers, France; INSERM, Research Unit 1082, 2 rue de la Milétrie, 86021, Poitiers, France; INSERM, CIC 1402, 2 rue de la Milétrie, 86021, Poitiers, France; Université de Poitiers, UFR de Médecine et Pharmacie, 6 rue de la Milétrie, 86073, Poitiers, France. 9. Laboratório de Endocrinologia Celular e Molecular (LIM-25), Faculdade de Medicina da Universidade de São Paulo (FMUSP), Avenida Dr. Arnaldo 455, CEP 01246903, São Paulo, SP, Brazil; Centro de Terapia Celular e Molecular (NUCEL/NETCEM) da FMUSP, Avenida Dr. Arnaldo 455, CEP 01246903, São Paulo, SP, Brazil. 10. INSERM, UMRS 1138, Centre de Recherche des Cordeliers, 15 rue de l'École de Médecine, 75006, Paris, France. Electronic address: gilberto.velho@inserm.fr.
Abstract
BACKGROUND AND AIM: Glutathione peroxidase (GPX) is a class of antioxidant enzymes that catalyze the reduction of hydrogen peroxide to water. GPX1 is the most abundant isoform and is expressed in all kidney cells. Isoprostane and advanced oxidation protein products (AOPP) were identified as markers of oxidative stress in patients with kidney disease. We investigated associations of GPX1 genotypes with kidney complications, and with plasma concentrations of isoprostane and AOPP in type 1 diabetic patients. METHODS: Four SNPs in the GPX1 gene region were genotyped in SURGENE (n=340; 10-year follow-up); GENEDIAB (n=461) and GENESIS (n=584) cohorts of type 1 diabetic patients. Subsets of GENEDIAB (n=237) and GENESIS (n=466) participants were followed up for 9 and 5years, respectively. Plasma concentrations of isoprostane and AOPP were measured at baseline in GENEDIAB. Hazard ratios (HR) were estimated for incidence of kidney complications. RESULTS: In SURGENE, 98 renal events (new cases of microalbuminuria or progression to more severe stage of diabetic nephropathy) occurred during follow-up. The minor T-allele of rs3448 was associated with the incidence of renal events (HR 1.81, 95% CI 1.16-2.84, p=0.008). In GENESIS/GENEDIAB pooled study, end stage renal disease (ESRD) occurred during follow-up in 52 individuals. The same variant was associated with the incidence of ESRD (HR 3.34, 95% CI, 1.69-6.98, p=0.0004). The variant was also associated with higher plasma isoprostane concentration in GENEDIAB cohort: 2.02±0.12 (TT+CT) vs 1.75±0.13 (CC) ng/mL (p=0.009), and with higher plasma AOPP in the subset of participants with the baseline history of ESRD (TT+CT 67±6 vs CC 48±6μmol/L, p=0.006). CONCLUSIONS: The minor T-allele of rs3448 was associated with kidney complications (incidences of microalbuminuria, renal events and ESRD) in patients with type 1 diabetes. The risk allele was associated with higher plasma concentrations of isoprostane and AOPP. Our results are consistent with the implication of GPX1 in the mechanism of renal protection against oxidative stress in type 1 diabetic patients.
BACKGROUND AND AIM: Glutathione peroxidase (GPX) is a class of antioxidant enzymes that catalyze the reduction of hydrogen peroxide to water. GPX1 is the most abundant isoform and is expressed in all kidney cells. Isoprostane and advanced oxidation protein products (AOPP) were identified as markers of oxidative stress in patients with kidney disease. We investigated associations of GPX1 genotypes with kidney complications, and with plasma concentrations of isoprostane and AOPP in type 1 diabeticpatients. METHODS: Four SNPs in the GPX1 gene region were genotyped in SURGENE (n=340; 10-year follow-up); GENEDIAB (n=461) and GENESIS (n=584) cohorts of type 1 diabeticpatients. Subsets of GENEDIAB (n=237) and GENESIS (n=466) participants were followed up for 9 and 5years, respectively. Plasma concentrations of isoprostane and AOPP were measured at baseline in GENEDIAB. Hazard ratios (HR) were estimated for incidence of kidney complications. RESULTS: In SURGENE, 98 renal events (new cases of microalbuminuria or progression to more severe stage of diabetic nephropathy) occurred during follow-up. The minor T-allele of rs3448 was associated with the incidence of renal events (HR 1.81, 95% CI 1.16-2.84, p=0.008). In GENESIS/GENEDIAB pooled study, end stage renal disease (ESRD) occurred during follow-up in 52 individuals. The same variant was associated with the incidence of ESRD (HR 3.34, 95% CI, 1.69-6.98, p=0.0004). The variant was also associated with higher plasma isoprostane concentration in GENEDIAB cohort: 2.02±0.12 (TT+CT) vs 1.75±0.13 (CC) ng/mL (p=0.009), and with higher plasma AOPP in the subset of participants with the baseline history of ESRD (TT+CT 67±6 vs CC 48±6μmol/L, p=0.006). CONCLUSIONS: The minor T-allele of rs3448 was associated with kidney complications (incidences of microalbuminuria, renal events and ESRD) in patients with type 1 diabetes. The risk allele was associated with higher plasma concentrations of isoprostane and AOPP. Our results are consistent with the implication of GPX1 in the mechanism of renal protection against oxidative stress in type 1 diabeticpatients.
Authors: Djurdja Jerotic; Marija Matic; Sonja Suvakov; Katarina Vucicevic; Tatjana Damjanovic; Ana Savic-Radojevic; Marija Pljesa-Ercegovac; Vesna Coric; Aleksandra Stefanovic; Jasmina Ivanisevic; Zorana Jelic-Ivanovic; Lana McClements; Nada Dimkovic; Tatjana Simic Journal: Toxins (Basel) Date: 2019-07-23 Impact factor: 4.546
Authors: Rebecca L Gould; Steven W Craig; Susan McClatchy; Gary A Churchill; Robert Pazdro Journal: Free Radic Biol Med Date: 2021-07-26 Impact factor: 8.101