Identification of a single nucleotide polymorphism indicative of high risk in acute myocardial infarction.

Background & objectives: Acute myocardial infarction (AMI) is a major health concern in India. The aim of the study was to identify single nucleotide polymorphisms (SNPs) associated with AMI in patients using dedicated chip and validating the identified SNPs on custom-designed chips using high-throughput microarray analysis. Methods: In pilot phase, 48 AMI patients and 48 healthy controls were screened for SNPs using human CVD55K BeadChip with 48,472 SNP probes on Illumina high-throughput microarray platform. The identified SNPs were validated by genotyping additional 160 patients and 179 controls using custom-made Illumina VeraCode GoldenGate Genotyping Assay. Analysis was carried out using PLINK software. Results: From the pilot phase, 98 SNPs present on 94 genes were identified with increased risk of AMI (odds ratio of 1.84-8.85, P=0.04861-0.003337). Five of these SNPs demonstrated association with AMI in the validation phase (P=0.05). Among these, one SNP rs9978223 on interferon gamma receptor 2 [IFNGR2, interferon (IFN)-gamma transducer 1] gene showed a significant association (P=0.00021) with AMI below Bonferroni corrected P value (P=0.00061). IFNGR2 is the second subunit of the receptor for IFN-gamma, an important cytokine in inflammatory reactions. Interpretation & conclusions: The study identified an SNP rs9978223 on IFNGR2 gene, associated with increased risk in AMI patient from India.

Levels of cathepsins in acute myocardial infarction.

AIMS/OBJECTIVE: Over expression of matrix degrading enzymes have been implicated in plaque destabilisation and rupture. Cathepsins associated with extracellular matrix breakdown make them intriguing suspects. The aim of the study was to analyse peripheral levels of cathepsin B and cathepsin K and their inhibitor cystatin C during acute myocardial infarction (AMI). MATERIALS AND METHODS: Study population included AMI patients at acute event (AMI group, n=48), stable angina patients (stable angina group n = 17), and healthy individuals (Control group, n=31). Cathepsin B, cathepsin K, cystatin C, and matrix metalloproteinases (MMP)-9 were analysed by enzyme-linked immunosorbent assay (ELISA) method. RESULTS: Cathepsin B (45.9%) and cathepsin K (92.31%) at acute event of myocardial infarction (AMI group) increased (P=0.001) while cystatin C decreased marginally (12.5%) as compared to controls. Stable angina group, demonstrated only marginal reduction in all the parameters studied as compared to controls. CONCLUSION: Cathepsin B and cathepsin K can be further evaluated as biomarkers in identifying high-risk individuals for AMI.

Soluble levels of cell adhesion molecules (CAMs) in coronary artery disease.

AIMS: To analyze soluble levels ofcell adhesion molecules (CAM) such as Intercellular CAM (ICAM), vascular CAM (VCAM-1), platelet endothelial CAM (PECAM-1), Endothelial (E)-selectin, and Platelet (P)-selectin in coronary artery disease patients and correlate with degree of severity of the disease. METHODS: Study population included patients who suffered myocardial infarction at presentation (N=49) and those with unstable angina (N=79) and stable angina (N=14). Soluble levels of CAMs were measured by ELISA. RESULTS: At acute event in AMI patients, there was significant rise of soluble (s) E-selectin (4.5 fold, P = 0.001), sVCAM-1 (65.6%, p = 0.001), sPECAM-1 (46.2%, p = 0.02), sP-selectin (42.7%, p = 0.001) and sICAM-1 (20.1%, p = 0.003) as compared to controls. In unstable angina group as compared to AMI there was significant decrease in the levels observed in, sE-selectin (62.7%, p = 0.001), sPECAM-1 (47.5%, p = 0.001) as well as sVCAM-1 (17.9%, p = 0.04) and insignificant decrease with respect to sICAM-1 and no change with respect to sP-selectin levels. Stable angina group as compared to unstable angina group demonstrated no significant difference in sCAMs and the trend with AMI group was similar to that seen between unstable angina and AMI group. Significantly elevated levels of sE-selectin, sVCAM-1 and sPECAM-1 at acute event suggest them to be causal molecules as well as markers of plaque destabilization. Levels of sP-selectin in stable angina were similar to that observed in AMI and unstable angina groups suggesting elevated platelet activation in stable angina as well.

Leucine125Valine (Leu125Val) Gene Polymorphism of Platelet Endothelial Cell Adhesion Molecule-1 (PECAM-1) and Myocardial Infarction in Indian Population.

Platelet-endothelial cell adhesion molecule-1 (PECAM-1) has role in atherosclerotic plaque development as well as in thrombosis leading to myocardial infarction (MI). Present study was aimed to analyse the association of PECAM-1 Leu125Val gene polymorphism with MI in Indian population. Subjects included healthy individuals as control (N = 116) and MI patients (N = 100) divided into two groups; MI patients at presentation of the acute event (MI-Group-1, N = 46) and patients with recent event of MI stabilized with treatment 4.5 days from their symptoms (MI-Group-2, N = 54). The difference in the distribution of Leu125Val genotype frequencies of controls and patients did not reach statistical significance. However Leu allele frequency (0.57) was more associated with MI patients as compared to control (0.504). sPECAM-1 levels were significantly elevated in patients at acute event of MI (MI-Group-1) by 44.1% (P = 0.009) as compared to controls and by 95.2% (P = 0.001) as compared to stabilized MI patients (MI-Group-2).

Role of matrix metalloproteinases in coronary artery disease.

AIM: Matrix metalloproteinases (MMPs) contribute both in the formation as well as in the destabilization of atherosclerotic plaque. In the present study we analyzed circulating levels of MMP-7 that acts on chondroitin sulphate a proteoglycan that is particularly abundant in atherosclerotic plaque and MMP-8 which acts on Type I collagen, the synthesis and degradation of which is important for stability of the plaque and correlate with the degree of severity of coronary artery disease (CAD). METHODS: Circulating levels of MMP-7 and MMP-8 and tissue inhibitors of MMP (TIMP) -1 and TIMP-2 were analysed by Enzyme Linked ImmunoSorbent Assay (ELISA7rpar;, in patients with acute myocardial infarction (AMI) at presentation (N=48), acute coronary syndrome (ACS) group (N=227rpar; (on treatment) and stable angina group (N=17) (on treatment). RESULTS: There was significant rise in MMP-8 (88.23%, P=0.001), in AMI group which decreased in ACS treated group 7lpar;15.9%, non-significant) as compared to controls. There was increasing trend of MMP-7 in AMI and ACS group and strong correlation with hsCRP. MMP-7 predominated in stable angina group. There was significant decrease in TIMP-2 in AMI group and TIMP-1 and TIMP-2 in ACS and stable angina group as compared to controls. CONCLUSION: Significant increase in MMP-8 and decrease in TIMP-2 during acute stage of AMI suggests MMP-8 and TIMP-2 are markers for vulnerable plaque independent of hsCRP for AMI. MMP-7 was found to be elevated in stable angina patients and was correlated with hsCRP at acute phase of AMI suggesting persistent at all stages of CAD.