Endothelial dysfunction plays an important role in the pathogenesis of diabetic vascular disease, including diabetic nephropathy (DN). Endothelial nitric oxide synthase (eNOS) gene polymorphisms that affect eNOS activity are associated with endothelial dysfunction. The aim of this study was to evaluate the association of three polymorphisms of the eNOS gene (894G>T, -786T>C, and 27-bp-VNTR) with the risk of DN among type 2 diabetic patients. A total of 400 type 2 diabetic patients were enrolled in this study. The DN group comprised 200 patients; the group of diabetics without nephropathy comprised another 200 patients. Genetic analysis for eNOS gene polymorphisms was done in all subjects. Measurement of nitric oxide levels was estimated. The C allele for -786T>C and the T allele for 894G>T were significantly more frequent in diabetics with nephropathy than in diabetics without nephropathy (p<0.001; odds ratio [OR] and 95% confidence interval [CI] for the C allele=1.64 [1.24-2.17] and p<0.001; OR and 95% CI=1.7 [1.27-2.26] for the T allele). The haplotypes CTa (with all the mutant alleles) and CTb were significantly more common in patients with DN (p=0.01 and 0.003, respectively). These results suggested that the eNOS polymorphisms might represent genetic determinants for developing DN in type 2 diabetic Egyptians.
Heat shock proteins with molecular weight 70 kDa (hsp70) are highly conserved immunogenic intracellular molecules. There are two main subtypes: one is expressed constitutively (hsc70), while the other is induced under stressful conditions (ihsp70). Using an ELISA directed against recombinant human ihsp70, antibody titers were determined in patients with defined ocular inflammatory conditions (Behçet's disease, Vogt-Koyanagi-Harada (VKH), pars planitis, and sarcoidosis) as well as in a group of age-matched normal volunteers. In comparison to healthy controls (n = 14, absorbance 0.269), levels were significantly elevated in Behçet's disease (n = 18; 0.412), sarcoidosis (n = 15; 0.432), and pars planitis (n = 13; 0.346), but not in VKH (n = 10; 0.263). A correlation was also noted for treatment versus no treatment in pars planitis (p = 0.028), but not in other inflammatory conditions. There was no correlation with the level of intraocular disease activity as defined by vitreous haze and vision drop. Since pars planitis is a purely ocular condition, circulating levels of ihsp antibodies likely reflect the extent of disease involvement within the eye.
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