Impact of c242T Polymorphism of p22phox in Diabetic type1 Nephropathy (NEPHRODIANOX)
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.
Type 1 Diabetes Mellitus
|Study Design:||Observational Model: Cohort
Time Perspective: Prospective
|Official Title:||Impact of c242T Polymorphism of p22phox in the Development of Diabetic Nephropathy,in Caucasian Diabetic Type 1 Patient.|
- comparison of prevalence of homozygous polymorphism between the DN-group and the non-DN group [ Time Frame: on day 1 ] [ Designated as safety issue: No ]
- comparison of polymorphism of p22phox between the ND group and the sub-group of non-ND patients with diabetic retinopathy only [ Time Frame: day 1 ] [ Designated as safety issue: No ]
- comparison of polymorphism prevalence between the 3 groups [ Time Frame: day 1 ] [ Designated as safety issue: No ]
- delay between diabetes diagnosis and ND onset by genetic polymorphism [ Time Frame: 20 years ] [ Designated as safety issue: No ]Kaplan Meier method
- albuminuria [ Time Frame: day 1 ] [ Designated as safety issue: No ]mg/day
- HbA1c [ Time Frame: day 1 ] [ Designated as safety issue: No ]HbA1c in %
Biospecimen Retention: Samples With DNA
We will include 60 patients to reach the required number. We take 2 blood samples: one for genetic analysis and one to determine HBA1c and plasma creatinine. We also take one urinary sample to determine the urinary albumine / creatinine ratio
|Study Start Date:||January 2011|
|Study Completion Date:||March 2013|
|Primary Completion Date:||March 2013 (Final data collection date for primary outcome measure)|
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
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01371955
|University Hospital of Grenoble|
|Grenoble, France, 38043|
|Principal Investigator:||BENHAMOU pierre yves, MD PhD||service de diabétologie|