Novel linkage of LMNA Single Nucleotide Polymorphism with Dilated Cardiomyopathy in an Indian case study.

BACKGROUND: Dilated Cardiomyopathy (DCM) is one of the most commonly encountered heart diseases reported globally. It is characterized by enlarged ventricles with impaired systolic and diastolic functions. Mutations in LMNA gene are one of the causative factors to precipitate the disease. However, association of SNPs of LMNA with DCM in particular has not been well documented. METHOD: Here we present a limited and restricted case study of patients from south eastern part of India afflicted with idiopathic DCM and conduction defects. By using next generation sequencing we have sequenced the exons of LMNA gene from genomic DNA isolated from patients. RESULT: We have identified the linkage of 8 different LMNA SNPs with idiopathic DCM viz. rs121117552, rs538089, rs505058, rs4641, rs646840, rs534807, rs80356803 and rs7339. These SNPs are scattered throughout the gene with prevalence for the region encoding the central rod domain of lamin A/C. CONCLUSION: Most of these SNPs in LMNA were previously reported to be involved in various disorders other than DCM. We conclude that, variation in LMNA is one of the major underlying genetic causes for the pathogenesis of DCM, as observed in few Indian populations.

Distribution of ABO blood group and major cardiovascular risk factors with coronary heart disease.

The purpose of this study is to establish whether ABO blood group is related to coronary heart disease in an individual in Asian Indian Bengali population of eastern part of India. Two hundred and fifty (250) CHD patients and two hundred and fifty (250) age and sex matched healthy subjects were enrolled in the study. ABO blood group distribution in patients was compared with control group. Frequency of major cardiac risk factors was determined to find any correlation between blood groups and cardiovascular risk factors. The distribution of ABO blood groups in patients versus control group was A in 24.00 versus 21.60%, B in 30.80 versus 32.40%, O in 38.40 versus 21.60%, and AB in 6.80 versus 24.40%. The analysis showed significant difference in frequency of O (OR = 1.857, 95%CI = 1.112-3.100, P = 0.018) and AB (OR = 0.447, 95%CI = 0.227-0.882, P = 0.020) blood group between healthy controls and CHD individuals. Our results may suggest that the AB blood group decreases the risk of CHD in healthy controls, and it might be due to the higher concentration of high density lipoprotein cholesterol (HDL-c), while the O blood group increases the risk of CHD due to lower HDL-c levels in Bengali population of eastern part of India.

Apolipoproteins AI/B/E gene polymorphism and their plasma levels in patients with coronary artery disease in a tertiary care-center of Eastern India.

AIM: The present study was designed to investigate whether the three-apolipoprotein (AI, B, E) gene polymorphisms were related to alter their plasma protein levels and hence associated to coronary artery disease (CAD). METHODS: We determined distribution of MspI apo AI, EcoRI apo B, HhaI apo E gene polymorphisms, plasma apolipoproteins and lipids levels among 150 patients having CAD admitted to the Department of Cardiology, N.R.S. Medical College & Hospital, Kolkata, India during June 2010-June 2012 and 150 age sex matched healthy controls. RESULTS: We found that ApoAI concentration of studied population was significantly different in each genotypes of -75 G/A apo AI (p < 0.0001) gene polymorphism. A significant association was found in multivariate analysis for the genotypes with apo E4 allele [odds ratio (OR): 3.639; 95% confidence interval (CI): 1.019-12.995, p = 0.040] with four conventional risk factors (i.e. smoking, low-density lipoprotein, ApoAI and ApoB) with CAD. In contrast E2 allele has reverse effect, but the genotypes with apo E2 allele was no longer significant in the multivariate model (OR: 1.788; 95% CI: 0.400-8.001, p = 0.447) where as being significant in univariate analysis (OR: 0.219; 95% CI: 0.087-0.552, p = 0.001). CONCLUSIONS: Our findings suggest that the polymorphisms apo AI MspI and apo B EcoRI do not seem to affect CAD. But the genotype with E4 allele of apo E gene independent of other risk factors is associated with this disease.

Relation of anti- to pro-inflammatory cytokine ratios with acute myocardial infarction.

BACKGROUND/AIMS: Acute myocardial infarction (AMI) is a leading cause of death. Inflammatory processes play an important role in atherosclerosis, which is intimately related to AMI. The aim of this study was to investigate the association between anti-inflammatory and pro-inflammatory cytokines ratios and AMI. METHODS: A total of 90 AMI patients and 90 age-and sex-matched controls were recruited in this study. Plasma cytokines and conventional risk factors were determined by standard methods. RESULTS: Patients with AMI showed increased interleukin (IL)-6 and tumor necrosis factor-alpha levels and lower anti- to pro-inflammatory cytokine ratios as compared with controls. A multivariate logistic regression analysis revealed that IL-10 to IL-6 ratio was independently associated with the occurrence of AMI (odds ratio [OR], 5.39; 95% confidence interval [CI], 2.39 to 12.17; p < 0.0001). In contrast, IL-6 levels were no longer significant in the multivariate model (OR, 1.02; 95% CI, 0.932 to 1.12; p = 0.603). A receiver operating characteristic (ROC) curve analysis indicated that IL-6 levels and IL-10 to IL-6 ratios were a significant predictor of AMI (area under ROC curve, 0.892 and 0.851, respectively). CONCLUSIONS: Our results suggest that the ratio of IL-10 to IL-6 is independently associated with AMI, and reduced levels of this ratio may favor the development of AMI.

Association of low-density lipoprotein particle size and ratio of different lipoproteins and apolipoproteins with coronary heart disease.

BACKGROUND: Worldwide coronary heart disease (CHD) is estimated to be the leading cause of death. Current knowledge about prevention of CHD is mainly derived from developed countries. Therefore, this study aimed to find out the association of CHD with ratios of different lipoproteins and apolipoproteins, LDL particle size, as well as different traditional risk factors in Asian Indian population in Eastern part of India. METHODS: Case-control study of 100 patients with CHD and 98 healthy controls were age and sex matched. After clinical evaluation, blood samples were collected for biochemical assays. RESULTS: Multivariate logistic regression analysis found apoB (OR 2.96; 95% CI 1.02-8.54), apoB/HDL-c (OR 4.14; 95% CI 1.33-12.83), nonHDL-c (OR 5.41; 95% CI 2.08-14.10), apoB/apoAI (OR 6.64; 95% CI 2.37-18.57), and LDL particle size (9.59; 95% CI 2.92-31.54) were independently associated with CHD. Area under the ROC curves derived from the model (AUROC 0.947; 95% CI 0.916-0.977) are significantly higher than any other variables. CONCLUSIONS: Findings from the multivariate analysis, apoB, apoB/HDL-c, nonHDL-c, apoB/apoAI, and LDL particle size are potent indicators and useful for diagnosis of predisposed CHD.