Is there any association between GLY82 ser polymorphism of rage gene and Turkish diabetic and non diabetic patients with coronary artery disease?

This study was carried out in 52 non-diabetic, 62 diabetic patients with coronary artery disease (CAD) and 55 controls. A Gly to Ser change RAGE gene was analyzed by PCR-RFLP techniques. GlyGly genotype frequency is higher in non-diabetics versus controls (P < 0.001). GlySer frequency is higher in diabetics than controls and non-diabetics (P < 0.001). Ser allele frequency is respectively increased in the order of diabetics > Controls > non-diabetics. These results reveals none association between Gly82Ser and the development of disease in non-diabetic patients. In diabetics with Ser allele, higher prevalence of left-ventricule-hypertrophy was observed, but the significant difference between Gly82Ser and left-ventricule-hypertrophy only found in the whole patient group. As a result Ser allele has much more importance in the development of left-ventricule-hypertrophy than other cardiovascular risk factors. In this study we found the presence of Gly allele contributes to the CAD in non-diabetics and Ser allele may contribute to disease in diabetics.

Associations of -374T/A polymorphism of receptor for advanced glycation end products (RAGE) gene in Turkish diabetic and non-diabetic patients with coronary artery disease.

BACKGROUND: In this study we aimed to determine the possible risks for the development of coronary artery disease (CAD) in diabetic (DM(+)) and non-diabetic (DM(-)) patients according to the -374T/A polymorphism of the receptor for advanced glycation end products (RAGE) gene which affects the function of RAGE itself. MATERIALS AND METHODS: This study was carried out in 52 non-diabetic and 62 diabetic patients with CAD, and 55 CAD-free, healthy volunteers as controls. The A-T transversion polymorphism at position -374 in the promotor region of the RAGE gene was analyzed by polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) techniques. RESULTS: The -374T/A AA genotype frequency was statistically higher in the whole patient group when compared with the control group (p=0.034), and statistically higher in the DM(+) group when compared with the control group (p=0.003). Homozygosity for the -374A allele was found to be higher, but not statistically meaningful, in DM(-) patients (17.3%) when compared with the control group (13.2%). In this study, in contrast with other studies, we found possesion of the A allele to be an independent risk factor in CAD in patients with diabetes mellitus. CONCLUSION: Possesion of the -374A allele may contribute to the CAD in diabetic patients with triggering macrophages by increased levels of AGEs.

Is LOX-1 K167N polymorphism protective for coronary artery disease?

BACKGROUND: Human lectin-like oxidized low-density lipoprotein receptor 1 (LOX-1, OLR1) has been identified as a cell surface endocytosis receptor for oxidized low-density lipoprotein (oxLDL) on vascular endothelial cells. OxLDLs are avidly ingested by macrophages, resulting in foam cell formation. OxLDLs are also involved in inducing smooth muscle cell migration, proliferation and transformation. A single nucleotide polymorphism K167N (G501C) of the LOX-1 gene results in an amino acid dimorphism (Lys/Asn) at residue 167. Replacement of this Lys residue causes reduced binding and internalization of oxLDL. The purpose of this study was to investigate the effect of the LOX-1 K167N gene polymorphism in Turkish patients with coronary artery disease (CAD). MATERIALS AND METHODS: K167N polymorphism were studied in 91 patients with CAD and 72 healthy controls by the PCR-RFLP method. RESULTS: The frequencies of the KK genotype and the K allele were higher in the CAD group than the controls (p<0.05), while the frequency of the NN genotype was higher in the control group than in the CAD group (p<0.05). It was observed that the decreased CAD risk in patients who had the N allele was reversed by male sex (OR: 0.400 -->0.481) and smoking (OR: 0.400 -->0.949). Although male sex and smoking were lower than other cardiovascular risk factors in patients with the N allele they were higher than other cardiovascular risk factors in patients with the K allele. CONCLUSION: Male sex and smoking decrease the protective effects of the N allele. The adverse effects of the K allele on the CAD risk resulting from the K167N polymorphism appear to be independent of other cardiovascular risk factors.

Results of adjunctive coronary endarterectomy in 548 patients.

Coronary endarterectomy is a controversial procedure that plays a particular role in the treatment of coronary artery disease. We retrospectively investigated the results for 548 patients who underwent coronary endarterectomy as an adjunctive therapy for coronary artery bypass graft surgery during the period between 1996 and 2004. We assessed short-term outcomes and identified risk factors for adverse outcomes. Mean patient age was 67.9 + 9.3 years and mean angina class was 2.7 + 0.3. The mean number of distal anastomoses was 3.8 + 1.1 patients (73.4%) had single and 151 (27.6%) multiple coronary artery endarterectomies. Of the 151 patients who underwent multiple endarterectomies, 97 (17.7%) had endarterectomies in 2 coronary arteries, 40 (7.2%) in 3 coronary arteries, 11 (2%) in 4 coronary arteries, 2 (0.36%) in 5 coronary arteries, and 1 (0.18%) in 6 coronary arteries. Postoperative mortality was 6.2% (34 patients). The predictors for early mortality were recent myocardial infarction and left ventricular dysfunction. Our results suggest that adjunctive coronary endarterectomy can be accomplished with acceptable results but with higher mortality rates than ordinary coronary artery bypass grafting. Adjunctive coronary endarterectomy should be considered as a last option for the surgical treatment of diffuse coronary disease.

The effect of NQO1 polymorphism on the inflammatory response in cardiopulmonary bypass.

Cardiopulmonary bypass (CPB) has been associated with systemic inflammatory response syndrome (SIRS). Endothelial dysfunction related to non-laminar flow during CPB is known to play a key role in this complex pathology. Antioxidant response element (ARE) dependent NAD(P)H:quinone oxidoreductase 1 (NQO1) promoter is a regulatory element involved in the anti-inflammatory mechanism in vasculature exposed to non-laminar flow. Mutation of the NQO1 could represent a novel anti-inflammatory effect in CPB. The goal of this study was to demonstrate whether genetic variants of NQO1 affect cytokine release after CPB. Eighteen patients who underwent standard coronary artery bypass grafting (CABG) operation were included in the study. Genotyping for NQO1 was performed. Serum Interleukin-6 (IL-6) levels were measured before induction, during CPB after declamping the aorta, and 24 h after operation. Clinical data were collected respectively. Seven patients were NQO1 T carriers and 11 patients were NQO1 T non-carriers. During CPB, IL-6 concentrations were increased in NQO1 T carriers compared to T non-carriers (p = 0.038). Although ventilation times and blood loss were higher in T carriers these were not statistically significant. Patients with NQO1 T carriers showed significantly higher IL-6 levels during CPB. Non-laminar flow during CPB may diminish the transcriptional activation of the NQO1 in T carriers. Preoperative determination of this novel anti-inflammatory mechanism could be useful to improve operative outcome in CPB.

Ischemic preconditioning and nicotinamide in spinal cord protection in an experimental model of transient aortic occlusion.

OBJECTIVES: Spinal cord injury is a devastating complication after aortic surgery. The aim of the present study is to examine the effects of ischemic preconditioning (IPC) and nicotinamide containing perfusate in transient aortic occlusion in the rat. METHODS: Thirty-two male Spraque-Dawley rats under general anesthesia were randomly assigned to four groups (n=8 in each group). The infrarenal aortas were clamped for 45 min. Groups were as follows: Group 1, undergoing occlusion but receiving no treatment. Group 2, had 5 min of IPC before occlusion. Group 3, received nicotinamide (0.2 ml/l) during the transient occlusion. Group 4, received combined IPC (5 min) and nicotinamide infusion during the transient occlusion. The rats were then allowed for recovery and were tested for their neurological status. All animals were sacrificed at the end of the 48 h and spinal cords also examined histologically. Anti- poly (ADP-ribose) polymerase p85 fragment pAb was used as an immunohistochemical marker for detection of apoptosis. RESULTS: In 24 h paraplegia represented as grade 0 and 1 occurred in six animals in Group 1 and two animals in Groups 2 and 3 and one in Group 4. In 48 h six animals in Group 1 and only one animal in Groups 2 and 3 showed a paraplegia. The incidence of neurologic deficit was significantly reduced in animals who had IPC and nicotinamide infusion (P<0.05). At 48 h, combined IPC and nicotinamide showed a significant benefit compared to nicotinamide but not to the IPC alone. Histologic examination of the spinal cords revealed that a neuronal necrosis contributes to acute spinal cord degeneration after a period of aortic occlusion and both nicotinamide and IPC have protective effects against neuronal necrosis. No difference was found among the groups. CONCLUSIONS: Both IPC and nicotinamide are beneficial in protection against neurological damage in transient aortic occlusion. IPC alone as expected is significantly beneficial both at 24 and 48 h compared to controls. At 24 h combined nicotinamide and IPC show significant benefit compared to only nicotinamide, but this difference is not maintained at 48 h.