Department Of Human Genetics And Molecular Medicine

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Author: search.filters.author.Kaul, Subhash

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    Association of APOE (E2, E3 and E4) gene variants and lipid levels in ischemic stroke, its subtypes and hemorrhagic stroke in a South Indian population
    (Elsevier Ireland Ltd, 2016) Das, Satrupa; Kaul, Subhash; Jyothy, Akka; Munshi, Anjana
    In the present study we evaluated the association of APOE (E2/E3/E4) polymorphism with ischemic stroke (n = 620), its subtypes and hemorrhagic stroke (n = 250) in a South Indian population from Telangana. The genotypes were determined using PCR-RFLP while lipid levels were measured using commercially available kits. We found significant difference in the genotypic distribution between hemorrhagic stroke patients and controls for certain genetic models [E2/E2 vs. E2/E4; E3/E3 vs. E2/E3; E3/E3 vs. E2/E4; E4/E4 vs. E2/E3; E4/E4 vs.E2/E4 and E3 vs. E4]. However, no significant difference was observed in genotypic distribution between ischemic stroke patients and controls. On analysing the genotypic distribution between ischemic and hemorrhagic stroke patients, statistically significant difference was observed in specific genetic models [E2/E2 vs. E2/E4; E3/E3 vs. E2/E3; E3/E3 vs. E2/E4; E4/E4 vs. E2/E3 and E4/E4 vs. E2/E4]. In ischemic stroke subtypes analysing for alleles E3 vs. E2 and E3 vs. E4, we found significant association with intracranial large artery (p = 0.01), cardioembolic stroke (p = 0.001 and p = 0.0004) and lacunar stroke (p = 0.02). Analysing the association of various genotypes with different lipid levels significant association was observed for VLDL (P = 0.000) and for triglyceride (P = 0.000) levels with E2/E4 and E3/E4 genotypes in ischemic stroke but not in hemorrhagic stroke. In conclusion, our results suggest that APOE polymorphism does seem to play a role in hemorrhagic stroke and also in the development of specific subtypes of ischemic stroke. Further, in ischemic stroke VLDL and triglycerides levels were found to be significantly associated with E2/E4 and E3/E4 genotypes. ? 2016 Elsevier Ireland Ltd.
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    CRP Gene (1059G>C) Polymorphism and Its Plasma Levels in Ischemic Stroke and Hemorrhagic Stroke in a South Indian Population
    (Springer New York LLC, 2014) Das, Satrupa; Roy, Sitara; Kaul, Subhash; Jyothy, Akka; Munshi, Anjana
    In the present study, we evaluated the association of 1059G>C polymorphism in C-reactive protein (CRP) gene with the risk of ischemic and hemorrhagic strokes. We did not find a significant association of this polymorphism with stroke. However, 2?% of mutants were observed in hemorrhagic stroke patients with a 0.01 frequency for the C allele. We also estimated the high-sensitivity C-reactive protein (hsCRP) levels in hemorrhagic stroke and compared the levels with our already published data on ischemic stroke. The hsCRP level in hemorrhagic stroke was found to be significantly elevated in comparison with that in controls (p < 0.001). However, there was no difference in the mean value of hsCRP levels between types of stroke. In conclusion, the G>C polymorphism in the promoter region of the CRP gene is not abundant in the population and cannot be connected with different hsCRP levels and stroke prediction. The CRP level is a useful marker in stroke, but cannot help in differentiating between types of stroke. ? 2014, Springer Science+Business Media New York.
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    E-selectin gene (S128R) polymorphism in hemorrhagic stroke: Comparison with ischemic stroke
    (Elsevier Ireland Ltd, 2014) Das, Satrupa; Roy, Sitara; Kaul, Subhash; Jyothy, Akka; Munshi, Anjana
    Increasing evidence suggests that genetic variation in inflammatory genes plays a pivotal role in pathogenesis of stroke. The aim of the present study was to evaluate the association of E-selectin S128R polymorphism with hemorrhagic stroke and also to evaluate the genotypic and allelic variation with ischemic stroke in a South Indian population from Andhra Pradesh. In this study, we recruited 250 hemorrhagic stroke patients along with 250 age and sex matched controls. The genotypes were determined using PCR-RFLP method and the strength of association between genotypes and hemorrhagic stroke was determined by odds ratio with 95% confidence interval (CI) and chi-square analysis. Allelic and genotypic frequencies of the polymorphism differed significantly between hemorrhagic stroke patients and controls (p < 0.001). Significant association was also found following dominant (p < 0.001) and co-dominant (p < 0.001) models. On comparing the genotypic and allelic frequencies between ischemic and hemorrhagic stroke significant difference was found between the two stroke types (p < 0.001). In conclusion, we found the AC genotype to be a significant risk factor for hemorrhagic stroke and we also found significant differences in AC genotype and C allele among the two stroke types. The genotypic and allelic variation between the ischemic and hemorrhagic stroke, suggests that E-selectin S128R mediated amplification of leukocytes onto endothelial cells, leading to secondary damage of brain cells is more pronounced in hemorrhagic stroke. ? 2014 Elsevier Ireland Ltd.
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    Genetic determinants in ischaemic stroke subtypes: Seven year findings and a review
    (Elsevier, 2015) Munshi, Anjana; Das,Satrupa.; Kaul, Subhash
    Stroke is a global health problem and a leading cause of disability worldwide. There have been numerable studies undertaking research on different aspects of ischaemic stroke employing various epidemiological, clinical and molecular parameters. Nevertheless ischaemic stroke being a complex disorder with different subtypes demands equal attention towards its subtypes too. Since there has been enough evidence that disposition to certain subtype is genetically determined and there is a distinct mechanism that influences its development, association studies should focus on subtypes simultaneously while studying specific genes. Data from such studies will thus provide better and intricate findings with regard to heterogenous ischaemic stroke. In the present review we discuss the genes studied by our group over a period of seven years in association with stroke subtypes in a South Indian population and correlate the findings with similar genetic studies from other populations so as to provide an overview of various genes involved in the pathogenesis of ischaemic stroke subtypes. ? 2014 Elsevier B.V.
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    MTHFR Gene (C677T) Polymorphism in Ischemic Stroke, its Subtypes and Hemorrhagic Stroke in a South Indian Population
    (2015) Das, Satrupa; Roy, Sitara; Kaul, Subhash; Jyothy, Akka; Munshi, Anjana
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    Association of ACE gene I/D polymorphism and ACE levels with hemorrhagic stroke: comparison with ischemic stroke
    (Springer-Verlag Italia s.r.l., 2015) Das, Satrupa; Roy, Sitara; Sharma,Vandana; Kaul, Subhash; Jyothy, Akka; Munshi, Anjana
    In the present study, we investigated the association of insertion/deletion polymorphism of ACE gene with genetic predisposition to hemorrhagic stroke and also determined the mean ACE activity levels in ischemic and hemorrhagic stroke patients. Two hundred hemorrhagic stroke, 200 ischemic stroke patients and 200 gender and age matched controls were recruited for the study. We found statistically significant difference in the genotypic distribution between hemorrhagic patients and controls for dominant, co-dominant and recessive models. Significant difference was observed in the allelic frequencies between hemorrhagic patients and controls. Multiple logistic regression analysis confirmed these findings [adjusted OR for DD genotype was 2.46 (95?% CI 1.43?4.21) and p?=?0.001] and [adjusted OR for ID genotype was 5.45 (95?% CI 2.6?10.4) and p?=?0.001]. We have already established the association of this polymorphism in ischemic stroke patients. Comparing hemorrhagic with ischemic stroke, we found a significant difference in genotypic distribution between the two [for II vs. DD, ?2?=?4.75; p?=?0.03, OR?=?0.5 (95?% CI 0.27?0.93) and for DD vs. ID, ?2?=?5.1; p?=?0.02, OR?=?1.8 (95?% CI 1.1?3.3)]. Our results indicate that DD genotype and D allele are important risk factors for the development of stroke. Individuals harboring DD genotype of ACE I/D polymorphism are more predisposed to hemorrhagic stroke than ischemic stroke. Further, the mean ACE activity level was found to be significantly higher in hemorrhagic and ischemic stroke in comparison with controls, but there was no significant difference in the levels found between the two types of stroke. ? 2014, Springer-Verlag Italia.
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    Association of -1382A>G CCL11 gene variant with ischemic stroke, its subtypes and hemorrhagic stroke in a South Indian population
    (Medknow Publications, 2014) Roy, Sitara; Das, Satrupa; Munshi, Anjana; Kaul, Subhash; Jyothy, Akka
    Conclusion: The results of the present study show that the GG genotype is a significant risk factor for ischemic as well as hemorrhagic stroke. Further, the frequency of the GG genotype was observed to be higher in hemorrhagic stroke patients in comparison with ischemic stroke. Evaluating the association with ischemic stroke subtypes, a significant association was observed with intracranial large artery atherosclerosis and lacunar stroke.Background: CCL11 (Eotaxin-1) is an important inflammatory cytokine belonging to the CC family of chemokines associated with a number of infection or inflammation-related diseases such as atherosclerosis and stroke. We investigated the association of CCL11 gene polymorphism rs4795895-1382A>G with ischemic and hemorrhagic stroke.Materials and Methods: Six hundred and twenty ischemic stroke patients, 620 age- and sex-matched healthy controls, and 220 hemorrhagic stroke patients, 220 age- and sex-matched healthy controls were included in the present study. The CCL11 gene polymorphism rs4795895-1382A>G was determined using PCR-RFLP technique.Results: We found a statistically significant difference in the genotypic distribution between ischemic stroke patients and controls (For GG vs. AA, ?2= 7.604; P < 0.001, Odds ratio = 2.793; 95% CI = 1.308-5.9). For GG vs. AA + AG, ?2= 44.8, P < 0.001, Odds ratio = 2.382 (95% CI = 1.842-3.081). A significant difference was observed in the frequency of G and A alleles in patients and controls (For G vs. A, ?2= 43.26; P < 0.001, Odds ratio = 2.127; 95% CI = 1.693-2.672). Statistically significant difference was observed in the genotypic distribution between hemorrhagic stroke patients and controls (For GG vs. AG, ?2= 26.78; P = 0.001, Odds ratio = 3.5; 95% CI = 2.162-5.824). A significant difference was observed in the frequency of G and A alleles in patients and controls (For G vs. A, ?2= 41.98; P = 0.001, Odds ratio = 4.1; 95% CI = 2.61-6.44).