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Master Thesis

Évaluation de polymorphismes de p22phox, RAGE et ALOX12 dans la survenue de la néphropathie diabétique chez le type 1‎ : projet NEPHRODIANOX

Abstract : Background: Oxidative stress is a key component of type 1 diabetic nephropathy. Therefore, we investigated the association between polymorphisms of three genes implicated in this pathway: C242T of CYBA (p22phox), -374T/A and -429T/C of RAGE, as Arg261Gln of ALOX 12, in the delay of microalbuminuria onset in type 1 diabetic patients. Methods: 162 diabetic type 1 patients with 32.9 +/- 9 years of diabetes duration were included at the Grenoble University Hospital. 53 presented a history of persistent microalbuminuria (> 30 mg/l) and 109 did not. Delay between microalbuminuria and diabetes diagnosis, as end stage renal disease (ESRD) onset and bio-clinical data, were recorded. Polymorphism status was determined and its association to microalbumuria was assessed with a Cox regression model. Results: All polymorphisms respect the Hardy Weinberg equilibrium. At univariate level, C242T dominant model (13.6% TT, 45.7% TC, 41.7% CC) and -374T/A (5.6% AA, 35.2% TA, 59% TT) were significantly correlated with microalbuminuria (p=0.038, 0.0021 respectively). The Cox regression model validated four significant variables: RAGE 374AA (HR 4.19 [1.84-9.58] (p=0.001)), p22phox TT+TC (HR 2.1 [1.16-3.8], p= 0.015), associated with male sex (HR 1.92 [1.07-3.43], p=0.028) and diabetes diagnosis at pediatric age (HR 1.85 [1.03-3.32], p=0.039). The same association was found with ESRD (p= 0.028 for p22phox TC+TT, and p=0.033 for RAGE 374AA). The C242T polymorphism was independent of retinopathy onset (66.7% of CC patients versus 63.6% of CT+TT p=0.6 for superiority and p=0.043 for non inferiority). Finally we suspected an increasing risk with polymorphism associations but it did not reach significant level. Conclusions: p22phox C242T, and RAGE-374T/A correlate with microalbuminuria onset in a type 1 diabetic French population. The same correlation with ESRD onset provides argument for the involvement of a genetic predisposition involving renal oxidative stress for diabetic nephropathy independently of retinopathy for C242T.
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Master Thesis
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https://dumas.ccsd.cnrs.fr/dumas-00874390
Contributor : Jean-Hugues Morneau <>
Submitted on : Thursday, October 17, 2013 - 4:49:30 PM
Last modification on : Tuesday, May 11, 2021 - 11:36:17 AM
Long-term archiving on: : Friday, April 7, 2017 - 12:55:36 PM

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  • HAL Id : dumas-00874390, version 1

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Benoit Franko. Évaluation de polymorphismes de p22phox, RAGE et ALOX12 dans la survenue de la néphropathie diabétique chez le type 1‎ : projet NEPHRODIANOX. Médecine humaine et pathologie. 2013. ⟨dumas-00874390⟩

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