Human Genetics And Molecular Medicine - Research Publications

Permanent URI for this collectionhttps://kr.cup.edu.in/handle/32116/107

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Author: search.filters.author.Munshi, AnjanaSubject: search.filters.subject.Genetic Association

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    Genetic signatures in ischemic stroke: Focus on aspirin resistance
    (Bentham Science Publishers B.V., 2017) Vasudeva, Kanika; Chaurasia, Pratibha; Singh, Sulena; Munshi, Anjana
    Background and Objective: Stroke is one of the leading causes of death. There has been compelling evidence that stroke has a genetic component. Genetic variants not only influence susceptibility to stroke but have also been found to alter the response to pharmacological agents and influence the clinical outcome of the disease. Stroke patients are treated with antiplatelet drugs like aspirin and clopidogrel to prevent a secondary stroke. In spite of the fact that many new antiplatelet drugs have been developed, aspirin is still considered as a golden standard for the antiplatelet therapy. Aspirin achieves its action by inhibiting platelet cyclooxygenase (COX) system involved in the formation of thromboxane A2 (TXA2). TXA2 triggers reactions leading to platelet activation and aggregation. This Non-steroidal anti-inflammatory drug (NSAID) acts by inhibiting this mediator. Despite the demonstrated benefits of aspirin, many patients develop secondary stroke or other vascular events, an observation that has led to the concept of aspirin resistance. Studies have demonstrated that adequate antiplatelet effects are not achieved in 5-45% patients suggesting that many individuals are aspirin resistant. Aspirin resistance is multifactorial in origin. A genetic component has also been suggested, and variants in more than a dozen genes involved in absorption, distribution, metabolism, excretion (ADME) and pharmacodynamics of aspirin have been shown to be responsible for aspirin resistance. In addition, the patients on aspirin treatment also face adverse drug reactions on account of genetic variation. Conclusion: The present review has been compiled with an aim to revisit all the studies related to genetic variation contributing to aspirin resistance as well as adverse drug reactions. The output of high throughput genomic technology like genome wide association studies and others has also been discussed. ? 2017 Bentham Science Publishers.
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    Association of the genetic variants of insulin receptor substrate 1 (IRS-1) with type 2 diabetes mellitus in a Saudi population
    (Humana Press Inc., 2014) Alharbi, Khalid Khalaf; Khan, Imran Ali; Munshi, Anjana; Alharbi, Fawiziah Khalaf; Al-Sheikh, Yazeed; Alnbaheen, May Salem
    Type 2 diabetes mellitus (T2DM) is a chronic degenerative disease, phenotypically and genetically heterogeneous, characterized by high levels of glucose and metabolic complications. Insulin receptor substrate 1 (IRS-1) plays a key role in the insulin-stimulated signal transduction pathway. A glycine-to-arginine substitution at codon 972 (G972R) (rs1801278) in the IRS-1 gene has been associated with impaired insulin action. Another SNP rs2943641 in the IRS-1 gene has been found to be associated with T2DM and insulin resistance in genome-wide association studies. The aim of the present study was to evaluate whether rs1801278 and rs2943641 are associated with increased risk of T2DM in the Saudi population. The study included 376 T2DM cases and 380 healthy controls. Genomic DNA was isolated using a commercially available kit supplied by Norgen Biotech Corp. Genotyping was performed by PCR and RFLP analysis. There was a significant difference in the genotypic distribution as well as allelic frequency between the T2DM cases and controls in case of both the polymorphisms for rs1801278 (1.752, 95?% CI 1.002?3.121; p?=?0.04), and for rs2943641 (OR?=?1.482, 95?% CI 1.176?1.867; p?=?0.001). In conclusion, both the (rs1801278 and rs2943641) polymorphisms are associated with T2DM in the Saudi population. ? 2014, Springer Science+Business Media New York.
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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.