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.

Sex-specific Association With Kidney Disease

Sponsors

Lead sponsor: University of Sao Paulo General Hospital

Source University of Sao Paulo General Hospital
Brief Summary

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

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.

Overall Status Completed
Start Date May 1994
Completion Date October 2012
Primary Completion Date May 1994
Study Type Observational
Primary Outcome
Measure Time Frame
Albumin to Creatinine Ratio Two Years
Enrollment 1396
Condition
Eligibility

Sampling method: Probability Sample

Criteria:

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).

Gender: All

Minimum age: 11 Years

Maximum age: N/A

Healthy volunteers: No

Overall Official
Location
facility Faculty of Medicine from University of São Paulo
Location Countries

Brazil

Verification Date

March 2013

Responsible Party

Responsible party type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Arm Group

Arm group label: Genesis French-Belgium Study

Description: 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.

Arm group label: GENEDIAB

Description: 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.

Arm group label: Brazilian cohort

Description: 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.

Study Design Info

Observational model: Case-Only

Time perspective: Cross-Sectional

Source: ClinicalTrials.gov