Sex-specific Association With Kidney Disease

Study Overview
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Brief Summary
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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.

Detailed Description
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In the present study, three cohorts of type 1 diabetic patients (one Brazilian and two French/Belgium cohorts) were studied for the association with diabetic nephropathy (DN) with a total of 1396 patients. The patients were classified according to the urinary albumin-to-creatinine ratio (ACR) or urinary albumin excretion rate (UAER) in absence of nephropathy, defined as ACR <30 mg/g or UAER < 20 µg/min or < 20 mg/L and plasma creatinine <1.7 mg/dL; incipient nephropathy, defined as persistent microalbuminuria (ACR 30 - 300 mg/g of creatinine or UAER 20 - 200 µg/min or 20 - 200 mg/L) and plasma creatinine <1.7 mg/dL; established diabetic nephropathy, defined as past or present macroalbuminuria (ACR >300 mg/g of creatinine or UAER >200 µg/min or > 200 mg/L) and plasma creatinine <1.7 mg/dL; advanced diabetic nephropathy, defined as past or present macroalbuminuria, plasma creatinine >1.7 mg/dL and any renal replacement therapy. Genotyping of polymorphisms was performed by Real Time PCR using fluorescent-labelled probes.

Official Title
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Sex-specific Associations of Variants in the Regulatory Regions of NADPH Oxidase-2 (CYBB) and Gluthatione Peroxidase 4 (GPX4) Genes With Kidney Disease in Type 1 Diabetes.

Conditions
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Diabetic Nephropathy

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Overt 10 years of Diabetes Mellitus (Brazilian cohort) Diagnostic of diabetes before the age of 35 years, with initial ketosis and requirement for permanent insulin treatment within 1 year of diagnosis and past or present diagnosis of diabetic retinopathy. (Genesis cohort). Diagnostic of diabetes before the age of 35 years and past or present diagnosis of severe diabetic retinopathy. (GENEDIAB cohort). Exclusion Criteria: Patients presenting autoimmune diseases, HIV or HCV infections (Brazilian cohort) Patients with glomerular filtration rate < 60 mL min-1 1.73 m2 without diabetic retinopathy (Brazilian cohort) Terminal cancer and personal disability (GENEDIAB cohort).

Ages Eligible for Study
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Minimum Age: 11 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Genesis French-Belgium Study<br>Cross-sectional, multi-center, binational (Belgian and France) study designed to evaluate the genetic components of diabetic nephropathy. It is a cohort with 501 patients, including 279 individuals (55.7%) with diagnosis of diabetic nephropathy. | |
| GENEDIAB<br>Cross-sectional, multi-center, binational (Belgian and France) study designed to evaluate the genetic components of diabetic nephropathy. It is a cohort with 444 patients, including 310 individuals (69.8%) with diagnosis of diabetic nephropathy. | |
| Brazilian cohort<br>The cohort comprised 451 patients with type 1 diabetes for more than 10 years (56% women; aged 36 ± 11 years, mean ± SD) recruited in diabetes/endocrinology departments of three university hospitals in the cities of São Paulo (SP), Campinas (SP) and Porto Alegre (RS), Brazil. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Albumin to Creatinine Ratio |  | Two Years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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oxidative stress, genetic susceptibility, GPX4, NOX2