The association of T786C and G894T polymorphisms of eNOS gene with diabetic retinopathy in Greece.

PURPOSE: To investigate whether eNOS T786C (rs2070744) and G894T (rs1799983) gene polymorphisms are associated with diabetic retinopathy in Greek diabetic patients. MATERIALS: 271 patients with type-2 diabetes mellitus participated in our study; 130 suffered from diabetic retinopathy and 141 not. All the patients underwent a complete ophthalmological examination, while clinical and demographic data were assessed. Furthermore, they were genotyped for rs2070744 and rs1799983 single nucleotide polymorphisms of eNOS gene. RESULTS: Regarding the clinical and demographic data, no significant differences were detected between the studied groups, except for hemoglobin A1c levels and the frequency of insulin treatment (higher in patients with diabetic retinopathy). The frequency of rs1799983 GT genotype was significantly elevated in patients with diabetic retinopathy (55% vs. 40%, P = 0.011) and was associated with a 2-fold increased risk of developing retinopathy (OR 1.92, 95% CI 1.16-3.17). Furthermore, we demonstrated that the aforementioned genotype was significantly and independently associated with increased odds for retinopathy onset in diabetic subjects (OR 2.23, 95% CI 1.28-3.90, P = 0.005), regardless of the impact of other confounders. CONCLUSIONS: We documented that rs1799983 GT genotype could be recognized as an independent risk factor of retinopathy in Greek patients with type-2 diabetes mellitus, while no role for rs2070744 polymorphism was identified. Further research in different ethnic groups will clarify the exact association of these polymorphisms with the risk for diabetic retinopathy development.

Polymorphism analysis of ADIPOQ gene in Greek patients with diabetic retinopathy.

BACKGROUND: Several genetic polymorphisms have been identified as risk factors for diabetic retinopathy (DR) onset. The purpose of our study was to determine whether ADIPOQ rs1501299 and rs2241766 gene polymorphisms are associated with DR in a cohort of Greek diabetic patients. MATERIALS AND METHODS: 218 patients with type-2 diabetes mellitus (T2DM) were included in the study; 109 suffered from DR and 109 not. All the participants underwent a complete ophthalmological examination, while clinical and demographic data were assessed. Furthermore, they were genotyped for G276T (rs1501299) and T45G (rs2241766) single nucleotide polymorphisms of ADIPOQ gene. RESULTS: Between the studied groups, no significant differences were detected regarding the demographic and clinical data (p > .05 for all), except for hemoglobin A1c levels and frequency of insulin treatment (higher in DR patients). We detected that the frequency of rs1501299 GT genotype was significantly elevated in DR patients (53% vs. 34%, p = .004) and was associated with a higher risk of developing retinopathy (OR 2.31, 95% CI 1.30-4.11). Furthermore, we demonstrated that the rs1501299 GT genotype was significantly and independently associated with increased odds for DR development in diabetic subjects (OR 2.68, 95% CI 1.38-5.21, p = .004), regardless of the impact of other known risk factors. CONCLUSIONS: We documented that rs1501299 GT genotype could be recognized as an independent risk factor of retinopathy in T2DM Greek patients, while no role for rs2241766 polymorphism was identified. Further research in different ethnic groups will clarify the exact association of these polymorphisms with the risk of DR development.

Associations between Adiponectin Gene Variability, Proinflammatory and Angiogenetic Markers: Implications for Microvascular Disease Development in Type 2 Diabetes Mellitus?

BACKGROUND: Adiponectin gene (ADIPOQ) variability may affect the risk for type 2 diabetes mellitus (T2DM) but it remains unclear whether it is involved in microvascular complications. OBJECTIVE: To explore the impact of ADIPOQ variability on markers of inflammation and angiogenesis in T2DM. METHODS: Overall, 220 consecutive T2DM patients from our outpatient diabetic clinic were genotyped for G276T (rs1501299) and T45G (rs2241766) single nucleotide polymorphisms of ADIPOQ gene. Serum levels of interleukin-6 (IL-6), intercellular adhesion molecule-1 (ICAM-1), vascular endothelial growth factor (VEGF) were measured by enzyme-linked immunosorbent assay and high sensitivity Creactive protein (hsCRP) by immunonephelometry. RESULTS: Homozygosity for the G allele on rs2241766 was associated with significantly lower serum VEGF and ICAM-1 levels compared with other genotype groups, but had no effect on IL-6. Genetic variability on rs1501299 was not associated with either VEGF or ICAM-1 levels, but T homozygotes for rs1501299 had significantly lower IL-6 concentrations compared with G carriers. Furthermore, the presence of the G allele on rs2241766 was associated with significantly lower HbA1c, whereas no associations were observed for both body mass index and hsCRP with either rs2241766 or rs1501299. CONCLUSION: Genetic variability on adiponectin gene was associated with serum levels of inflammatory and angiogenetic markers. Further research is required to elucidate the role of adiponectin in the development and/or progression of microvascular disease in T2DM patients.

Syphilis infection in an HIV patient presenting with leukemoid reaction: Case report and review of the literature.

Leukemoid reaction (LR) is an uncommon though dreadful sign for the treating physician, as it is related to increased mortality. In the few series that have addressed its incidence and clinical significance, infectious causes count for about half of the cases of LR, the rest accounting for cancer, drugs or rarer causes. In the HIV setting, it represents an even rarer event, owing probably to the impaired granulocytic response of AIDS patients to bacterial agents. However no report exists as to the incidence of LR to the immune-restored HIV patients adequately treated with antiretroviral therapy (ART). Syphilis is a well known cause of mild lymphocytosis, though only one report of LR exists in the congenital setting. We hereby report a case of an HIV patient adequately treated with ART, who presented with LR with a lymphomonocytic preponderance after infection with treponema pallidum.

MicroRNAs: Novel diagnostic and prognostic biomarkers in atherosclerosis.

MicroRNAs (miRNAs) are an emerging class of highly conserved, non-coding small RNAs that regulate gene expression on the post-transcriptional level by inhibiting the translation of protein from mRNA or by promoting the degradation of mRNA. The involvement of miRNAs in the regulation of lipid metabolism, inflammatory response, cell cycle progression and proliferation, oxidative stress, platelet activation, endothelial function, angiogenesis and plaque formation and rapture indicates important roles in the initiation and progression of atherosclerosis. In the light of this evidence we will review the role of miRNAs in atherosclerosis.

MicroRNAs in cardiovascular therapeutics.

Recent research reveals the crucial role microRNAs (miRNAs) in the pathogenesis and progression of many pathological conditions, including cardiovascular diseases. It is widely documented that miRNAs represent critical regulators of cardiovascular function and participate in almost all aspects of cardiovascular biology. In particular, they are involved in several pathophysiological pathways of various manifestations of cardiovascular disease, such as coronary artery disease, heart failure, stroke, diabetes mellitus, arterial hypertension and cardiac arrhythmias. In the present article we review the available literature regarding to the role of miRNAs in certain cardiovascular conditions. Moreover, we discuss the therapeutic potential of miRNAs for treating cardiovascular diseases and we attempt to highlight future directions.

Serum osteoprotegerin and osteopontin levels are associated with arterial stiffness and the presence and severity of coronary artery disease.

BACKGROUND: Osteopontin (OPN) and osteoprotegerin (OPG) have recently emerged as key factors in both vascular remodeling and development of atherosclerosis. Arterial stiffness has an independent predictive value for cardiovascular events. We evaluate the relationship between OPG, OPN serum levels and vascular function in coronary artery disease (CAD) patients. METHODS: The study population was consisted of 409 subjects (280 with CAD and 129 without CAD). Carotid-femoral pulse wave velocity (PWV) was measured as an index of aortic stiffness. OPG and OPN levels were measured, as markers of vascular remodeling and calcification, by ELISA. Gensini score was used to evaluate the extent of CAD. RESULTS: CAD patients, compared to those without CAD, had higher OPG (3.91 ± 1.87 pmol/l vs. 2.88 ± 1.32 pmol/l, p<0.001) and logOPN levels (1.81 ± 0.18 ng/ml vs. 1.71 ± 0.24 ng/ml, p<0.001) and impaired PWV (8.94 ± 2.21 m/s vs. 8.28 ± 1.91 m/s, p=0.006). Furthermore, PWV was associated with serum OPG levels (r=0.19, p<0.001) and with serum logOPN levels (r=0.10, p=0.049). Multivariate linear regression analysis revealed that increased OPG (p=0.013) and logOPN (p=0.006) levels are associated with 3-vessel CAD and Gensini score (p=0.04 for OPG and p=0.09 for OPN), independently of other known cardiovascular risk factors. CONCLUSION: The present study revealed that serum OPG and OPN levels are positively associated with arterial stiffness, and with the extent of CAD. These preliminary results suggest that OPG and OPN levels are significantly correlated with vascular function contributing to the pathogenesis of atherosclerosis in CAD. Further studies are needed to explore the mechanisms of action of OPG and OPN in CAD.