RESUMEN
The aim of our study was to investigate an association between polymorphisms of either the VEGF (vascular endothelial growth factor) gene (rs6921438) or the KDR (kinase insert domain receptor) gene (rs2071559, rs2305948) and DN (diabetic nephropathy) in Caucasians with T2DM (type 2 diabetes mellitus). The second aim was to investigate the effect of either the VEGF gene (rs6921438) or the KDR gene (rs2071559, rs2305948) on the immune expression of either VEGF or KDR in the renal tissues of T2DM subjects (to test the functional significance of tested polymorphisms). The study included 897 Caucasians with T2DM for at least ten years (344 patients with DN and 553 patients without DN). Each subject was genotyped and analyzed for KDR (rs1617640, rs2305948) and VEGF (rs6921438) polymorphisms. Kidney tissue samples taken from 15 subjects with T2DM (autopsy material) were immunohistochemically stained for the expression of VEGF and KDR. We found that the rs2071559 KDR gene was associated with an increased risk of DN. In addition, the GG genotype of the rs6921438 VEGF gene had a protective effect. We found a significantly higher numerical area density of VEGF-positive cells in T2DM subjects with the A allele of the rs6921438-VEGF compared to the homozygotes for wild type G allele (7.0 ± 2.4/0.1 mm2 vs. 1.24 ± 0.5/0.1 mm2, respectively; p < 0.001). Moreover, a significantly higher numerical area density of KDR-positive cells was found in T2DM subjects with the C allele of rs2071559 (CC + CT genotypes) compared to the homozygotes for wild type T allele (9.7± 3.2/0.1 mm2 vs. 1.14 ± 0.5/0.1 mm2, respectively; p < 0.001) To conclude, our study showed that the presence of the C allele of the rs2071559 KDR gene was associated with a higher risk of DN, while the G allele of the rs6921438-VEGF conferred protection against DN in Slovenian T2DM subjects.
Asunto(s)
Diabetes Mellitus Tipo 2 , Nefropatías Diabéticas , Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple , Factor A de Crecimiento Endotelial Vascular , Receptor 2 de Factores de Crecimiento Endotelial Vascular , Población Blanca , Humanos , Receptor 2 de Factores de Crecimiento Endotelial Vascular/genética , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/complicaciones , Masculino , Factor A de Crecimiento Endotelial Vascular/genética , Femenino , Nefropatías Diabéticas/genética , Nefropatías Diabéticas/patología , Persona de Mediana Edad , Población Blanca/genética , Anciano , Genotipo , Frecuencia de los Genes , AlelosRESUMEN
Smad proteins influence the TGFß signaling pathway, which plays an important role in the progression of atherosclerosis. The aim of our study was to investigate the association between the rs17228212 polymorphism of the SMAD3 gene and advanced carotid atherosclerosis in Slovenian subjects and to investigate the effect of the rs17228212 SMAD3 polymorphism on the expression of SMAD3 in endarterectomy sequesters. In this cross-sectional case-control study, 881 unrelated Caucasians were divided into two groups. The first group included 308 patients with advanced carotid atherosclerosis of the common or internal carotid artery with stenosis greater than 75% that underwent a revascularization procedure (cases). The control group consisted of 573 subjects without hemodynamically significant carotid atherosclerosis. We analyzed the rs17228212 polymorphism of the SMAD3 gene using the StepOne real-time polymerase chain reaction system and TaqMan SNP genotyping assay. The results in the two genetic models showed a statistically significant association, codominant (OR 4.05; CI 1.10-17.75; p = 0.037) and dominant (OR 3.60; CI 1.15-15.45; p = 0.045). An immunohistochemical analysis of SMAD3 expression was conducted for 26 endarterectomy specimens. The T allele of the rs17228212 SMAD3 gene was shown to be associated with an increased numerical area density of SMAD3-positive cells in carotid plaques.
RESUMEN
BACKGROUND: A disintegrin and metalloprotease with thrombospondin motif 7 (ADAMTS-7) was reported to play a role in the migration of vascular smooth muscle cells and neointimal formation. The object of the study was to investigate the association between the rs3825807 polymorphism of ADAMTS7 and myocardial infarction among patients with type 2 diabetes mellitus in a Slovenian cohort. METHODS: 1590 Slovenian patients with type 2 diabetes mellitus were enrolled in this retrospective cross-sectional case-control study. In total, 463 had a history of recent myocardial infarction, and 1127 of the subjects in the control group had no clinical signs of coronary artery disease. Genetic analysis of an rs3825807 polymorphism of ADAMTS7 was performed with logistic regression. RESULTS: Patients with the AA genotype had a higher prevalence of myocardial infarction than those in the control group in recessive [odds ratio (OR) 1.647; confidence interval (CI) 1.120-2.407; p = 0.011] and co-dominant (OR 2.153; CI 1.215-3.968; p = 0.011) genetic models. CONCLUSION: We found a statistically significant association between rs3825807 and myocardial infarction in a cohort of Slovenian patients with type 2 diabetes mellitus. We report that the AA genotype might be a genetic risk factor for myocardial infarction.