miRNA polymorphisms and risk of premature coronary artery disease.

OBJECTIVE: Several microRNA (miRNA) polymorphisms have been associated with susceptibility to specific health disorders, including cardiovascular diseases. The aim of the present study was to investigate whether four well-studied miRNA polymorphisms in non-Caucasian populations, namely miR146a G>C (rs2910164), miR149 C>T (rs2292832), miR196a2 C>T (rs11614913) and miR499 A>G (rs3746444), contribute to the risk for the development of premature Coronary Artery Disease (CAD) in the Greek population. METHODS: We used a case-control study to examine these associations in 400 individuals: 200 CAD patients [including a subgroup of myocardial infraction (MI) patients] and 200 healthy controls, all of Greek origin. MiRNA polymorphisms were genotyped using three different assays: Polymerase chain reaction - restriction fragment length polymorphism (PCR-RFLP), High resolution Melting (HRM) and Sanger sequencing. RESULTS: Two of these polymorphisms, miR196a2 C>T (rs11614913) and miR499 A>G (rs3746444) were found to be strongly associated with increased risk for CAD (p=0.0388 and p=0.0013, respectively) and for MI (p=0.0281 and p=0.0273, respectively). Furthermore, miR146C-miR149C-miR196T-miR499G allele combination appeared to be significantly related to CAD (p=0.0185) and MI (p=0.0337) prevalence. CONCLUSIONS: Our results suggest that at least two of the studied polymorphisms, miR196a2 C>T (rs11614913) and miR499 A>G (rs3746444), as well as the miR146C-miR149C-miR196T-miR499G allele combination could represent useful biomarkers of CAD and/or MI susceptibility in the Greek population. These special genetic characteristics, in combination with environmental factors and personal habits, might contribute to CAD and/or MI prevalence.

Study on the admission levels of circulating cell-free DNA in patients with acute myocardial infarction using different quantification methods.

Circulating cell-free DNA (cf-DNA) is present in human biological fluids, mainly in plasma and serum, originating from cell death, a process that massively takes place during acute myocardial infarction (AMI). In the present study, cf-DNA was assessed by different quantification techniques, in order to determine its levels in patients admitted with AMI. A total of 130 subjects were included in the study: 80 ST elevation myocardial infarction (STEMI) patients and 50 healthy controls. Cf-DNA extracted from plasma was analyzed by: a) Qubit 3.0 with single (ss) and double (ds) stranded DNA assay kits, b) NanoDrop and c) quantitative PCR (qPCR). Cf-DNA levels were recorded elevated in AMI patients compared to those of healthy individuals. Specifically, Qubit 3.0 ss-DNA kit provided the highest cf-DNA concentration values for all the samples analyzed in comparison with ds-DNA assay kit and NanoDrop, approaching the values obtained by qPCR. Cf-DNA augments in massive cell death settings, including AMI, proposing that the quantification of its levels by novel methodologies could contribute to patient diagnosis and clinical management.

Expression of miR-208b and miR-499 in Greek Patients with Acute Myocardial Infarction.

BACKGROUND/AIM: Certain microRNAs (miRs) present in human plasma are candidate biomarkers for cardiovascular diseases, including acute myocardial infarction (AMI). We examined the expression of two cardiac-specific miRs (miR-208b and miR-499) in a Greek pathological population. MATERIALS AND METHODS: Plasma samples from AMI patients and healthy subjects (controls) were analyzed using TaqMan® MicroRNA assays. RESULTS: The concentration of both miRs was significantly elevated in AMI patients compared to healthy controls. Moreover, receiver-operating characteristic (ROC) curve analysis showed that miR-208b and miR-499 displayed similar properties with the established AMI biomarker cardiac troponin T (cTnT). CONCLUSION: We showed, for the first time, that these miRs could be used as AMI biomarkers in our population as well. Our data are in agreement with those of studies based on different population groups and further strengthen the observation that plasma levels of circulating miR-208b and miR-499 could serve as potential AMI biomarkers.

Conversion efficacy of intravenous ibutilide compared with intravenous amiodarone in patients with recent-onset atrial fibrillation and atrial flutter.

AIM: The aim of our study was to compare the efficacy and safety of ibutilide and amiodarone (intravenously) in converting recent-onset atrial fibrillation (AF) and atrial flutter (Af) to sinus rhythm (SR). METHODS: The study was prospective, randomized and included 152 (103 men and 49 women) consecutive patients with AF or Af of 3-48 h duration. Ibutilide is a selective class III antiarrhythmic agent which when administered intravenously can terminate AF and Af. Amiodarone is also a class III antiarrhythmic agent that when given intravenously or orally has proved to be more effective than other agents in terminating AF and Af [B.N. Singh, F.V. Mody, B. Lopez, J.S. Sarma. Antiarrhythmic agents for atrial fibrillation: focus on prolonging atrial repolarization. Am J Cardiol 1999 Nov 4; 84: 161R-173R.]. Seventy-nine patients (56 with AF and 23 with Af) that consisted group A were treated with ibutilide. Seventy-three (52 with AF and 21 with Af) consisted group B and were treated with intravenous infusion of amiodarone. RESULTS: The conversion rate of group A (ibutilide) was significantly higher than the conversion rate of group B (amiodarone) (80% vs. 57%, p=0.0054). As regards the kind of arrhythmia separately, for AF there wasn't significant difference (77% vs. 69%, p=ns) whereas for Af ibutilide was superior to amiodarone (87% vs. 29%, p=0.003). The conversion rates of ibutilide didn't differ for AF and Af (77% vs. 87%, p=ns). CONCLUSIONS: Ibutilide is more effective than amiodarone in converting recent-onset Af to SR whereas both drugs are equally effective in converting recent-onset AF to SR.