Browsing by Author "Sharma,Vandana"

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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.
Association of Xmn1 -158 γG variant with severity and HbF levels in β-thalassemia major and sickle cell anaemia
(Springer Netherlands, 2014) Dadheech,Sneha; Jain,Suman; Madhulatha,D.; Sharma,Vandana; Joseph,James; Jyothy, Akka.; Munshi, Anjana
Haemoglobinopathies including ?-thalassemia and sickle cell anaemia (SCA) are considered to be classical monogenic diseases. There is considerable clinical variability between patients inheriting identical ?-globin mutations. The reasons for this variability are not well understood. Previous studies have suggested that a variety of genetic determents influence different clinical phenotypes. The genetic variants that modulate HbF levels have a very strong impact on ameliorating the clinical phenotype. In the present study 6,500 blood samples from suspected cases were analysed using HPLC, ARMS-PCR, RDB techniques. Patients with ?-thalassemia and SCA were classified into mild, moderate, severe according to the severity score based on Hb levels, age of onset, age at which patients received their first blood transfusion, the degree of growth retardation and splenectomy. Patients with ?-thalassemia and SCA were analysed for Xmn1 polymorphism and association between this polymorphism and severity of ?-thalassemia and SCA was evaluated. We found a significant difference in genotypic and allelic frequencies of Xmn1 polymorphism between mild and moderate and mild and severe cases. There was a significant difference in high and low percentage of HbF in CC, CT and TT bearing individuals. The TT bearing individuals were found to have a high percentage of HbF in ?-thalassemia as well as SCA. This study confirms that increased ?G-globin expression associated with Xmn1 polymorphism ameliorates the clinical severity in ?-thalassemia as well as SCA in the study population. ? 2014, Springer Science+Business Media Dordrecht.
Genetic signatures in the treatment of stroke
(Bentham Science Publishers B.V., 2015) Munshi, Anjana; Sharma,Vandana
Stroke is the fourth leading cause of mortality and neurological disability. It is caused by an intricate interplay of environmental and genetic factors. Genes not only influence susceptibility to stroke but have also been found to alter the response to pharmacological agents and may also influence the clinical outcome of the disease. Current treatment strategies for stroke include tissue plasminogen activator, antiplatelet agents and lipid lowering drugs. These act via diverse mechanisms of actions and are centered around the management of modifiable risk factors to prevent the recurrent stroke events. However, a significant number of patients experience poor clinical outcome due to recurrent stroke events and drug induced adverse reactions. Therefore, accurate risk management and targeted prevention strategies remain yet to be explored at the level of individual patients with stroke. Pharmacogenetic based research studies have identified the relation between genetic factors and inter-individual variability towards drug treatment. Several single nucleotide polymorphisms in genes encoding for metabolizers, transporters and target receptors have been reported to influence the pharmacokinetics and pharmacodynamics of drugs used in the treatment of stroke. Many candidate gene studies have investigated the role of genetic variants in association with altered drug response in stroke treatment. However, these results are limited to clinical trials and should be replicated in Genome Wide Association (GWAS) Studies. In addition to this long term follow up prospective studies would be helpful in predicting drug induced risk/benefit ratio. Pharmacogenetic studies will reveal the correlation between variation in drug responses on the basis of the individual?s genomic profile better known as Personalized or Individualized Medicines. This will also optimize risk assessment and will stratify the population requiring careful attention before prescribing a particular medicine to achieve maximum therapeutic benefit. Moreover, this will help in designing the novel therapeutic agents with a targeted approach. In this concern, the Genomics and Randomized Trials Network (GARNET) has been created, which is a Pharmacogenomics Consortium aimed to identify genetic variants affecting an individual's response to treatment with the help of advanced technology. This review will address the major issues of therapeutic failures concerned with existing drugs used in the treatment of stroke and the need for exploring new and targeted therapeutic strategies based on pharmacogenetics. ? 2015 Bentham Science Publishers.