Impact of c242T Polymorphism of p22phox in Diabetic type1 Nephropathy (NEPHRODIANOX)

Impact of c242T Polymorphism of p22phox in the Development of Diabetic Nephropathy,in Caucasian Diabetic Type 1 Patient.

The physiopathology of diabetic nephropathy (DN) is unclear. To investigate risk factor, the investigators choose to look about some oxidative stress genes. Today a one-gene explanation is not really possible. So the theory of some genetic predisposition to DN is more likely.

The aim of the study is to look about the association of the C282T polymorphism of P22phox, a sub unit of the nicotinamide adenine dinucleotide phosphate-oxidase (NADPH oxidase) in the occurrence of DN. To follow the oxidative stress pathway of the DN, the investigators also investigate three other polymorphisms: -429 T/C, -374 T/A polymorphism of advanced glycation end-products receptor (AGER) and the p.Arg261Gln polymorphism of the 12 lipoxygenase (ALOX 12). Discordant data suggest a link between the first 2 polymorphisms and DN. The last polymorphism is correlated to albuminuria in diabetic patients.

Study Overview

• Status: Completed
• Conditions: Diabetic Nephropathy; Type 1 Diabetes Mellitus

Detailed Description

To avoid confounding factors, we choose type 1 diabetic patients. We plan, with the data of literature a number need to be significative with a power of 80% and an Alpha risk at 5%, the inclusion of 160 patients for our primary analyze of p 22 phox. Those patients are included consequentially from the diabetic consultation of the university hospital of Grenoble, if they have a history of more than 20 years of diabetes. Those patients have been separated according to the existence of DN, and their polymorphism. Then we estimate with the Fisher test the prevalence of DN in risky patient, and the prevalence of the risky phenotype in the nephropathic patients. Then we investigate with the same statistical test the -429 T/C,he -374 T/A AGER and p.Arg261Gln 12 ALOX polymorphisms.

• Study Type: Observational
• Enrollment (Actual): 162

Contacts and Locations

Study Locations

• France
  • Grenoble, France, 38043
    • University hospital of Grenoble

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

caucasian diabetic type 1 patients with more than 20 years of diabetes duration

Description

Inclusion Criteria:

• caucasian
• diabetic type 1
• older than 18 years old
• written consent

Exclusion Criteria:

• other etiology of diabetic nephropathy
• pregnancy
• other type of diabetes

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
diabetic nephropathy group; patient with diabetic nephropathy, defined as Albuminuria > 30 mg/day or urinary Albumine/ creatinine ratio > 3 mg/mmol ; or GFR estimated by MDRD less than 60 ml/min.1,73m². With no other etiology of diabetic nephropathy.
diabetic retinopathy group; patient with diabetic retinopathy defined as showing at least one micro aneurysm on retinography. Without nephropathy defined as above
no complication group; patient without diabetic nephropathy or retinopathy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
comparison of prevalence of homozygous polymorphism between the DN-group and the non-DN group	on day 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
comparison of polymorphism of p22phox between the ND group and the sub-group of non-ND patients with diabetic retinopathy only		day 1
comparison of polymorphism prevalence between the 3 groups		day 1
delay between diabetes diagnosis and ND onset by genetic polymorphism	Kaplan Meier method	20 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
albuminuria	mg/day	day 1
HbA1c	HbA1c in %	day 1

Collaborators and Investigators

• Sponsor: University Hospital, Grenoble
• Investigators: Principal Investigator: BENHAMOU pierre yves, MD PhD, service de diabétologie

Study record dates

Study Major Dates

• Study Start: January 1, 2011
• Primary Completion (Actual): March 1, 2013
• Study Completion (Actual): March 1, 2013

Study Registration Dates

• First Submitted: June 10, 2011
• First Submitted That Met QC Criteria: June 10, 2011
• First Posted (Estimate): June 13, 2011

Study Record Updates

• Last Update Posted (Estimate): November 15, 2013
• Last Update Submitted That Met QC Criteria: November 14, 2013
• Last Verified: November 1, 2013

More Information

Terms related to this study

• Keywords: genetic; diabetic nephropathy; RAGE; CYBA; p22phox; 12LOX; Type 1 Diabetes Mellitus with Diabetic Dermatitis; caucasian; more than twenty years of diabetes duration; older than 18 years; no nephropathy other than diabetic nephropathy
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Urologic Diseases; Endocrine System Diseases; Diabetes Complications; Diabetes Mellitus; Kidney Diseases; Diabetes Mellitus, Type 1; Diabetic Nephropathies
• Other Study ID Numbers: 1020; 2010-A01074-35 (Registry Identifier: ID RCB)