Publications (3)6.34 Total impact
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ABSTRACT: We investigated the involvement of chemotactic cytokine receptor 5 (CCR5) gene polymorphism in microvascular complications of T2DM. All subjects were genotyped with the 59029 SNP in the CCR5 gene. The genotype/allele frequencies did not differ between T2DM patients and controls. Genotype distribution was compared in patients with and without complications (nephropathy, retinopathy and neuropathy). The frequency of A allele was significantly higher in patients with complications (OR for A allele 3.07, 95% CI 2.49-3.77). The A allele carriage was associated with diabetic nephropathy (OR 6.17, 95% CI 3.28-11.6). An association was observed between 59029 polymorphism and age at T2DM onset. The A allele was more frequent in early onset than in late onset patients. For AA homozygotes OR was 2.38 (1.19-4.76) and 2.26 (1.12-4.58) in complicated and uncomplicated subgroups, respectively. These results suggest that CCR5 gene polymorphism is associated with diabetic nephropathy in T2DM.
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ABSTRACT: Renalase is a novel, recently identified, flavin adenine dinucleotide-dependent amine oxidase. It is secreted by the kidney and metabolizes circulating catecholamines. Renalase has significant hemodynamic effects, therefore it is likely to participate in the regulation of cardiovascular function.The aim of our study was to investigate the involvement of renalase gene polymorphisms in hypertension in type 2 diabetes patients. A total of 892 patients and 400 controls were genotyped with three SNPs in the renalase gene. The C allele of rs2296545 SNP was associated with hypertension (P < 0.01). For rs2576178 SNP, frequencies in hypertensive patients differed from controls, but not from normotensive patients. For rs10887800 SNP, the differences in the G allele frequencies were observed in hypertensive patients with stroke, with 66% of patients being GG homozygotes. To confirm observed association we later genotyped 130 stroke patients without diabetes. The OR for risk allele was 1.79 (95% CI 1.33-2.41). In conclusion, the renalase gene polymorphism was associated with hypertension in type 2 diabetes patients. The most interesting result is a strong association of the rs10887800 polymorphism with stroke in patients with and without diabetes. The G allele of this polymorphism might thus be useful in identifying diabetes patients at increased risk of stroke.
Article: Diabetes - Basic research[Show abstract] [Hide abstract]
ABSTRACT: INTRODUCTION AND AIMS: Evidence suggests that immunity plays a role in development and progression of diabetes complications, including nephropathy. In diabetic patients, increased levels of circulating immunoglobulins (IgG) and immune complexes (ICs) against proteins modified by diabetes were found associated with proteinuria and cardiovascular risk. We investigated the contribution of IgG receptors (FcγRs) to diabetic nephropathy progression in a model of accelerated type 1 diabetes, the diabetic apolipoprotein E deficient (apoE-/-) mouse. METHODS: We generated double knockout (DKO) mice with gene deficiency in apoE and γ-chain, the common subunit of activating FcγRs. Male mice (apoE-/-, DKO and wild-type) were made diabetic by streptozotocin injection. After 15 weeks, biochemical parameters, albuminuria, histomorphometry, gene expression, and oxidative stress were examined. The effects of FcγR deficiency were studied in cultured mesangial cells (MCs) stimulated with ICs. RESULTS: Compared with apoE-/-, diabetic DKO mice exhibited similar hyperglycemia and hypercholesterolemia, but reduced albuminuria and serum creatinine in association with a decreased mesangial matrix expansion and normalization of collagen and α-smooth muscle actin content. Furthermore, renal expression of genes involved in leukocyte infiltration (adhesion molecules and chemokines) and fibrosis (extracellular matrix proteins and growth factors), as well as oxidative stress, were all significantly reduced in diabetic DKO mice. In vitro, MCs from DKO mice failed to respond to ICs, as shown by reduced gene expression and NADPH oxidase-dependent superoxide generation. CONCLUSIONS: Functional deficiency in activating FcγRs alleviated renal hypertrophy, inflammation, and fibrosis in diabetic apoE-/- mice, thus indicating potential renoprotective effect of FcγR modulation in diabetes.
Medical University of Lublin
Lyublin, Lublin Voivodeship, Poland
- Laboratory of DNA Analysis and Molecular Diagnostics