Modifier Genes in Hypertrophic Cardiomyopathy Patients of South Indian Cohort (original) (raw)
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Implication of hsp70 gene polymorphisms in Arrhythmogenic right ventricular cardiomyopathy/dysplasia
JOURNAL OF HEART AND CARDIOLOGY, 2015
Introduction: Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is characterized by initial fibrofatty replacement of the right ventricle. Mutations in the Desmosomal and non desmosomal apart from modifier genes are known to be involved in the pathogenesis of the ARVC/D. One such modifier gene identified is HSP70 which plays an important role in cardio-protection. The present study investigates the role of Hsp70 polymorphisms in ARVC/D disease severity. Methods: Analysis of 100 control samples and 33 ARVC/D patients for 3 polymorphic loci was carried out by PCR-RFLP. Statistical analysis was carried out by SNPSTAT and haploview to analyze the genotypic data generated. Results: Our study revealed a statistically significant association of GC genotype (HSP70-1 +190G/C) [OR 2.93,95%CI 1.08-8.00, p=0.035] and TC genotype (HSP70-hom +2437T/C) [OR 2.04, 95% CI 1.01-4.55, p=0.045] with risk to develop ARVC/D. The haplotype frequency of CGT was also found to be higher in patients compared to controls, strengthening the synergistic effect of HSP70 family in ARVC/D. Conclusions: The present investigation revealed the importance of HSP70 polymorphisms in the pathogenesis of the ARVC/D. The results highlight a modifier role of HSP70 polymorphisms in ARVC/D etiopathogenesis, as the synergistic action of these polymorphisms may inhibit the HSP70 protein to perform its regular role, which in turn may trigger inflammation and apoptosis, hence the muscle tissue may be replaced by fibrofatty tissue.
Gene Polymorphisms in the TNF Locus and the Risk of Myocardial Infarction
Thrombosis Research, 2000
of polymorphisms in the TNF locus with major risk factors for CAD may exist, and should be explored We investigated two genetic polymorphisms in the in larger studies. © 2000 Elsevier Science Ltd. All tumor necrosis factor locus (TNF-␣ Ϫ308 G→A rights reserved. and LT-␣ ϩ252 A→G) as risk factors for coronary atherothrombotic disease (CAD) by determining its prevalence in 148 survivors of myocardial in-
Relationship between tumor necrosis factor-α (TNFA) gene polymorphisms and cardiac sarcoidosis
In vivo, 2014
Identification of genetic predisposition to cardiac sarcoidosis could play a critical role in the detection of sub-clinical forms of the disease. The aim of this study was to investigate the possible correlations between the emergence of cardiac sarcoidosis and the -1.031T/C, -857C/T, -308G/A, and -238G/A Tumor Necrosis Factor-α (TNFA) polymorphisms in a well-defined Greek cohort. One-hundred and seventy-three patients of Greek origin with sarcoidosis were recruited in the present study. Cardiac sarcoidosis was determined according to established criteria. Blood samples were collected and the TNFA polymorphisms were genotyped. No significant difference was noted between the patients with cardiac involvement and those without, concerning the -1.031T/C and -238G/A TNFA polymorphisms. Regarding the -857C/T polymorphism, the TT genotype and the T allele were found to be over-represented in patients with cardiac involvement (p=0.02 and 0.012, respectively). AA genotype of the -308G/A as ...
Research in Molecular Medicine
Introduction: Tumor necrosis factor alpha is a proinflammatory cytokine that initiates a polyvalent initial response of inflammatory cells, which is facilitated by coronary atherosclerosis. Further, it appears that the polymorphism and susceptibility to atherosclerosis are related to the TNF-α gene promoter. Aim: To assay single nucleotide polymorphisms of the TNF-α gene promoter in two sites (863 and 308) in atherosclerotic patients referred to Fatemeh al-Zahra Hospital. Materials and Methods: This case-control study was conducted on 120 patients (with stenosis greater than 50%) and 120 healthy individuals (with stenosis lesser than 10%). Genomic DNA was extracted using the Phenol-chloroform procedure from their white blood cells. Genotypes of these individuals and TNF-α gene polymorphisms were analyzed by the RFLP-PCR method. Genotype frequencies, the Hardy-Weinberg equilibrium test, and chi-square analysis were conducted using the SPSS software version 22. Results: Genotype frequencies of GA, GG, and AA in position-308 of the TNF-α gene of patients were 12.5%, 75%, and 12.5%, respectively; in healthy subjects, they were 7.5%, 21.7%, and 70.8%, respectively. Allele A to G allele increased the risk of disease by 12.716%. The genotype frequencies of AC, CC, and AA in position-863 of the TNFα gene of patients were 3.3%, 69.2%, and 27.5%, respectively; in healthy individuals, they were 2.5%, 11.7%, and 85.8%, respectively. Allele A to C allele increased the risk of disease by 16.373%. Statistical analysis revealed a significant correlation between the risk of atherosclerosis with single nucleotide polymorphisms in the TNF-α gene-863 at C <
Journal of Advanced Biotechnology and Experimental Therapeutics, 2021
ABSTRACT: Tumor necrosis factor-alpha (TNF-α) is a major cytokine for inflammatory response in human body. This is also well linked with obesity and causing different pathophysiological problems in type 2 diabetic mellitus (T2DM) patients because of its pro-inflammatory over expression. However, seemingly harmless nucleotide changes in the promoter region often cause oscillation in expression, results in complications like dyslipidemia and atherosclerosis that ultimately exploit to coronary heart disease (CHD). Therefore, this study was designed to evaluate association between TNF-α (-308G>A) polymorphism at promoter region and CHD in T2DM patients from the northern region (Rajshahi) of Bangladesh. The total number of participants was 96 T2DM patients. TNF-α polymorphism were detected using high resolution melting (HRM) curve analysis. A total of 32 participants were suffering from CHD and 8 polymorphism (3 homozygous and 5 heterozygous) were detected among them. From Fisher's Exact test, we found significant (P < 0.05) relationship between TNF-α (-308G>A) polymorphism and CHD in T2DM patients. According to Kendall's Tau correlation matrix (r = 0.218), there is a good correlation between target polymorphism and CHD. Therefore, the overall results suggest that TNF-α promoter (-308G>A) polymorphism influences CHD in T2DM patients.
Diagnostic Pathology, 2012
Coronary artery disease (CAD) is a multifactorial disease where genetic and environmental factors interact in complex ways to cause the disease. Heat shock protein genes are involved in the progress of CAD. This implies that genetic variants of Hsp70-2 genes might contribute to the development of the CAD. Aim of study: The aim of this study was to characterize statistical correlation of linkage between lipid profiles, polymorphism PstI site of Hsp70-2 gene and CAD. Patients and methods: This study was carried out on Tunisian patients with CAD recruited from Hospital of Fattouma Bourguiba of Monastir-Tunisia. Polymerase chain reaction and restriction enzymes were used to determine the genotypic distributions in 252 unrelated patients and 151 healthy control subjects. Further, ApoA-I and ApoB as well as the serum total of cholesterol, HDL, triglyceride, and hs-CRP levels were measured. Results: We showed a decreased level of ApoA-I, whereas the levels of each of ApoB and hs-CRP were increased in patients with CAD compared with control group. In addition our studies of a polymorphic PstI site of Hsp70-2 gene at position 1267 of the Hsp70-2 gene have revealed that the allelic frequency of P2 was significantly more frequent in CAD patients than controls group (p=0.007, OR=1.495). The genotypic distribution showed a high incidence of P2/P2 genotype in CAD patients (0.190) compared to healthy control (0.009) with reach significant difference (p=0.006). The P2 carriers showed a significantly increased of Total-Cholesterol (CT) and C-reactive protein (hs-CRP) levels in CAD patients (p=0.008 and p=0.018, respectively). Conclusion: The high incidence of P2-Hsp70-2 genotype in CAD patients and the significantly association of P2/P2 genotype with elevated Total Cholesterol and hs-CRP levels, supported that P2-Hsp70-2 genotype has susceptibility implication in CAD and could increased the risk of CAD in Tunisian population. Virtual slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/ vs/1118340895703689
Human Molecular Genetics, 1999
Tumour necrosis factor-α α α α (TNF-α α α α) plays a key role in orchestrating the complex events involved in inflammation and immunity. Accordingly, TNF-α α α α has been implicated in a wide range of autoimmune and infectious diseases, but also in conditions such as obesity and insulin resistance. The regulation of TNF-α α α α expression in man is indicated to be partly genetically determined. We therefore screened a 1263 bp section of the proximal promoter of the TNF-α α α α gene for common genetic variants affecting the transcriptional activity of the gene. Here we report the characterization of a common functional polymorphism in the promoter region of the TNF-α α α α gene, a C→ → → →A substitution at position-863. Electromobility shift assays provided evidence for a distinct difference in the binding of monocytic and hepatic nuclear factors to the-863C and-863A alleles. The rare-863A allele was associated with 31% lower transcriptional activity (P < 0.001) in chloramphenicol acetyltransferase (CAT) reporter gene studies in human hepatoblastoma (HepG2) cells, indicating that the-863C/A polymorphism influences the basal rate of transcription of the TNF-α α α α gene in vitro. Allele frequencies were 0.83/ 0.17 amongst 254 apparently healthy men of Swedish origin, aged 35-50 years. In 156 men, the-863C/A polymorphism was associated with the serum TNF-α α α α concentration, carriers of the rare A allele having a significantly lower TNF-α α α α level (P < 0.05). It is concluded that the common-863C/A polymorphism in the promoter region of the TNF-α α α α gene is functional in vitro in monocytic and hepatic cells and influences the serum TNF-α α α α concentration in vivo in healthy middle-aged men.
Background: Cardiovascular diseases (CVD) are important causes of death worldwide. Atherosclerosis is a chronic inflammatory disorder. It is the major cause of CVD and is manifested by ischemic heart disease or coronary artery disease (CAD). TNF-α is a pro-inflammatory cytokine that regulates immune response and promotes the development of atherosclerosis. Cytochrome p450 1B1 (CYP1B1) is an enzyme involved in the metabolism of endogenous and exogenous substrates. Objectives: This study aimed at examining the association of TNF-α rs1800629 G >A and CYP1B1 rs1056827 G>T gene polymorphisms with CAD susceptibility in an Indian cohort. Methods: AS-PCR and direct DNA sequencing were used to examine the association of TNF-α rs1800629 G >A and CYP1B1 rs1056827 G>T gene polymorphism with CAD in an Indian cohort. A total of 100 clinically confirmed cases of CAD and 110 matched apparently healthy controls were genotyped. Results: Allelic and genotypic frequencies did not deviate from Hardy-Weinberg equilibrium in the controls (p>0.05) for TNF-α G-308A and CYP1B1 rs1056827G>A. There was no significant difference between the TNF-α rs1800629 A>G genotype distribution between cases and controls (P-value >0.05). A significant difference was observed between the CYP1B1 rs1056827 G>T genotype distribution between CAD cases and controls (P<0.0003). Our result indicated that in the codominant model, the GA genotype of the CYP1B1 rs1056827 G>T was associated with CAD with OR= 2.21(1.17 to 4.15), RR=1.38(1.07 to 1.78), and P<0.013. In the dominant model, the (GA+AA) genotype was associated with CAD with OR=2.79(1.54 to 5.05) and P<0.007. The CYP1B1 rs1056827 'A' allele was associated with CAD with OR = 2.30 (1.55 to 3.42) and P< 0.0001. Our results indicated that TNF-α 1800629 gene polymorphism was strongly associated with hypercholesteremia (P<0.0009), HDL (P<0.0001), TGL (P<0.039), hypertension (P<0.0001), and smoking (P<0.0001) in patients with Coronary Artery Disease. Similar correlations of CYP1B1 rs1056827 genotypes were reported with cholesterol (P<0.020), HDL (P<0.002), LDL (P<0.006), hypertension (P<0.03), and smoking (P<0.005). Conclusion: It was reported that the GA genotype of the CYP1B1 rs1056827 G>T was strongly associated with susceptibility to Coronary Artery Disease with OR= 2.21(1.17 to 4.15)) and P<0.013, and similarly, its A allele was associated with predisposition to CAD with OR = 2.30(1.55 to 3.42) and P< 0.0001. Our results indicated that TNF-α 1800629 gene polymorphism is not associated with predisposition to Coronary Artery Disease. Nevertheless, these results should be taken with caution and further validated with larger-scale studies before being introduced in the clinical setting.
Clinical and Experimental Immunology, 2007
Summary Tumour necrosis factor (TNF)-α, an important proinflammatory cytokine, has been implicated in the pathogenesis of sarcoidosis, a multi-systemic granulomatous disorder of unknown aetiology. Here, we report for the first time the association of TNF haplotypes and genotypes with sarcoidosis and its prognosis in the Indian population. Five potentially functional promoter polymorphisms in the TNFA gene and a LTA_NcoI polymorphism (+252 position) of the LTA gene were genotyped in a clinically well-defined cohort of North-Indian patients with sarcoidosis (n = 96) and their regional controls (n = 155). Serum TNF-α (sTNF-α) and serum angiotensin converting enzyme (SACE) levels were measured and correlated with genotypes and haplotypes. The TNFA_-1031 and TNFA_-863 polymorphisms were identified as markers for disease onset (FET P = 0·006 and 0·042 for TNFA_-1031 and TNFA_-863, respectively). Additionally, the allele A of LTA_NcoI polymorphism was shown to be prevalent in the ‘no treat...