Association of the p22phox Component of NAD(P)H Oxidase With Susceptibility to Diabetic Nephropathy in Patients With Type 1 Diabetes

• DOI: 10.2337/diacare.26.11.3111
• Publication Date: 2007-03-05T22:51:27Z
• Authors: Andrea D. Hodgkinson; Beverley A. Millward; Andrew G. Demaine
• Keywords: Pathogenesis; Polyol pathway; P22phox; NAD(P)H oxidase

OBJECTIVE—Increased production of reactive oxygen species (ROS) in diabetes is thought to play a major role the pathogenesis diabetic microvascular complications such as nephropathy and retinopathy. The NAD(P)H oxidase complex an important source ROS vasculature. p22 subunit polymorphic with C242T variant that changes histidine-72 for tyrosine potential heme binding site, together A640G 3′ untranslated region. aim was investigate frequency these polymorphisms 268 patients type 1 or without complications. RESEARCH DESIGN AND METHODS—There highly significant increase T/T242 genotype compared those retinopathy alone no disease after 20 years’ duration (uncomplicated) normal healthy control subjects (33.3 vs. 6.5, 5.7, 0.0%, respectively, P < 0.000001). Furthermore, T242/G640 haplotype found 39.4% but only 26.5% 15.3 10.6% uncomplicated subjects, respectively. RESULTS—When variants were analyzed aldose reductase (5′ALR2) susceptibility genotypes, >46.0% possessed T242 allele Z-2 5′ALR2 11.2% (P 0.00003). CONCLUSIONS—In conclusion, results suggest polyol pathway may contribute nephropathy.