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  • Article: Influence of gelatinase B polymorphic variants and its serum levels in atherosclerosis.
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    ABSTRACT: Atherosclerosis, the underlying pathology of cardiovascular disease, is a common, multifactorial disorder with both genetic and environmental components as risk factors. Gelatinase B, also known as MMP-9, is one of the matrix metalloproteinases that is highly expressed in the disruption-prone regions of atherosclerotic plaques. It has been hypothesized that a genetic variation affecting the expression or activity of MMP-9 influences the susceptibility and progression of atherosclerosis. The present study aims to ascertain the polymorphic variants of the MMP-9 gene promoter and its serum levels, which contribute to interindividual differences in susceptibility to atherosclerosis. The study population consisted of 200 individuals who include 100 cases with angiographically recorded coronary artery disease (CAD) and 100 age- and sex-matched healthy controls. Serum levels of MMP-9 were determined in these subjects using an enzyme-linked immunosorbent assay, and polymorphic genotypes of MMP-9 were determined by the polymerase chain reaction-restriction fragment length polymorphism assay. The MMP-9 levels among subjects with the TT genotype for controls (12.21±2.39) and CAD (22.86±2.45) were significantly higher than that of CC genotype (controls 10.37±1.42 and CAD 16.44±7.99), and the values were intermediate for the CT genotype (control 11.21±2.01 and CAD 18.80±3.17) and found to be significant at p<0.01. Genotypic analysis of -1562C/T polymorphism among patients and controls showed higher T allele frequencies in the patient group (0.36) than in the controls (0.29). It has been observed that increased MMP-9 expression in T allele carriers may contribute to the severity of coronary atherosclerosis. These findings not only are relevant to the understanding of the pathogenesis of atherosclerosis but also may provide a novel target for future development of predictive, preventive, and therapeutic measures.
    Genetic Testing and Molecular Biomarkers 07/2012; 16(8):850-4. · 1.11 Impact Factor
  • Article: IL-10 high producing genotype predisposes HIV infected individuals to TB infection.
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    ABSTRACT: Interleukin (IL-10), an anti-inflammatory cytokine, is known to have dual effect on the host immune system. One of these roles is that it provides an effective autoregulatory mechanism which protects the host from excessive inflammation and tissue damage which is in part initiated by the Th1 driven pro-inflammatory immune responses during infections (such as TB, HIV and malaria). However, though beneficial, this autoregulatory mechanism is at times exploited by pathogens which evade elimination by Th1 driven immune response leading to chronic infections. The main aim of this study therefore was to study the influence of IL-10 polymorphism in relation to its levels with respect to HIV-TB co-infection. A total of 452 participants were categorized into HIV (121), active tuberculosis (TB) (118), HIV-TB (HT) (106) groups and healthy control group (107). Polymorphism for IL-10 gene (positions -1082, -819, -592) was studied using ARMS-PCR, RFLP. IL-10 and IFN-γ levels in antigen stimulated cultures were measured using ELISA. Statistical analysis was performed using Chi-Square (χ(2)) test, One-way ANOVA and t-tests. IL-10 (-1082) GG genotype was positively associated with HIV-TB, whereas AG with HIV and AA with TB. The cohort with GG genotype also had significantly high stimulated levels of IL-10 compared to AG and AA. AC genotype was significantly frequent in HIV-TB group at IL-10 (-592) position when compared with controls. HIV positive individuals with GG genotype at IL-10 (-1082) position and high IL-10 levels may have a high risk of developing TB co-infection.
    Human immunology 04/2012; 73(6):605-11. · 2.55 Impact Factor
  • Article: CD38 expression on CD8+ cells—Its influence on development of tuberculosis in HIV positive individuals
    Open Journal of Immunology. 04/2012;
  • Article: Endothelin-1 and endothelial nitric oxide polymorphisms in idiopathic pulmonary arterial hypertension.
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    ABSTRACT: Idiopathic Pulmonary arterial hypertension (IPAH) is a debilitating disease associated with very poor prognosis. The disease is characterised by endothelial dysfunction, smooth muscle proliferation and insitu thrombosis in the pulmonary artery, eventually leading to right ventricular failure. Two of the key endothelial mediators implicated in the pathogenesis of IPAH are endothelin-1 (EDN1) and nitric oxide (NO). EDN1 is a potent endogenous vasoconstrictor whereas NO is a vasodilator. In the present study screening of the EDN1 gene (EDN1) and NOS3 polymorphisms was taken up, to evaluate their association with IPAH. A significant association of EDN1 3A/4A polymorphism (+138 A; rs10478694) (OR-3.485; CI-1.254, 9.999; p=0.013) and EDN1 Lys198Asn polymorphism (G/T, rs5370) (OR-3.378, CI-1.104, 10.582; p=0.03) with IPAH was observed. Our results indicate that EDN1 polymorphisms in interaction with other genetic markers may play a significant role in individual's susceptibility to the disease and its clinical progression.
    International Journal of Molecular Epidemiology and Genetics 01/2010; 1(3):208-13.
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    Article: Risk factors for coronary heart disease in type II diabetes mellitus.
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    ABSTRACT: Cardiovascular complications are the major cause of morbidity and mortality in diabetic patients. An attempt has been made to evaluate the risk factors for coronary heart disease in type II diabetics. In the present study the levels of fasting and postprandial plasma glucose, total cholesterol, low density lipoproteins, triglycerides were high and the levels of high density lipoproteins were low in the type II diabetics compared to controls. The markers of free radical induced injury i.e. malondialdehyde and nitrite/nitrate were high while total antioxidant status a marker for antioxidant protection against reactive oxygen species was low in diabetics compared to controls. The study therefore suggests the importance of assessing these markers of oxidative stress and antioxidant capacity along with the other routine investigations in diabetic patients for initiating antioxidant therapy in addition to primary and secondary preventive measures to mitigate the devastating consequences of diabetes leading to coronary heart disease.
    Indian Journal of Clinical Biochemistry 07/2005; 20(2):75-80.

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