Please use this identifier to cite or link to this item: http://prr.hec.gov.pk/jspui/handle/123456789/14870
Title: Cyclo-Oxygenase Genetic Polymorphism & Its Correlation with Aspirin Resistance in Pakistani Population
Authors: Noor, Lt Col Dr Mudassar
Keywords: Biological & Medical Sciences
Pharmacology
Issue Date: 2020
Publisher: National University of Medical Sciences, Rawalpindi
Abstract: Aspirin is most widely used antiplatelet drug around the globe for the treatment of ischemic vascular diseases. Unfortunately, intake of this drug does not guarantee the hundred percent effective prevention from ischemic vascular event and patient may end up with adverse ischemic event despite regular administration of aspirin. This phenomenon is denoted as aspirin resistance. Studies have reported upto 70 percent prevalence of aspirin resistance. Genetic polymorphism of cyclooxygenase enzymes is one of the possible explanations which may lead to poor aspirin response. Objectives The current study was planned to investigate the incidence of aspirin resistance and its association with cyclooxygenase (COX1 rs1330344 and COX2 rs20417) polymorphism in Pakistan. Study design This cross sectional analytical study was carried out on ischemic heart disease patients who had been taking daily aspirin for atleast last the seven days. Sample size was 384. Platelet aggregation studies were performed by light transmitter aggregometer with arachidonic acid used as an agonist to determine the aspirin response of the patients. Salting out method was employed for the DNA extraction. Genotyping for SNP rs1330344 (COX1) and SNP rs20417 (COX2) was performed by polymerase chain reaction-restriction fragment length polymorphism and DNA fragments were visualized by agarose gel electrophoresis under UV light. The results of genotyping were correlated with the aspirin response status of patients. iv Results In the current research 13.8% (n=53) ischemic heart disease patients were found to be aspirin resistant where as 86.2% (n=331) patients were aspirin responders. The genotyping of COX1 SNP rs1330344 demonstrated that 24.21% (n=93), 57.81% (n=222) and 17.96% (n=69) of patients were carriers of wild type allele (CC), heterogeneous carriers (CT) and homogeneous carriers (TT) respectively. Whereas the genotyping of COX2 SNP rs20417 showed that 55.46% (n=213), 34.11% (n=131), 10.41% (n=40) of patients were carriers of wild type allele (GG), heterogeneous carriers (CG) and homogeneous carriers (CC) respectively. Statistical analysis did not demonstrate significant association of any of the allele of the two evaluated SNPs with aspirin resistance, p > 0.05. We found a positive association between aspirin resistance and smoking, p < 0.001. Conclusion The findings of our project support the phenomenon of aspirin resistance. We established that antiplatelet efficacy of aspirin is not persistent in each individual and 12.8% of our population may be poor responders to this drug. Unlike other demographic factors, smoking was found to be associated with inadequate antiplatelet actions of aspirin. Our genotypic findings confirm the presence of SNPs of COX1(rs1330344) and COX2 (rs20147) genes, moreover none of these SNPs contributed in the existence of aspirin resistance in our population.
Gov't Doc #: 20207
URI: http://prr.hec.gov.pk/jspui/handle/123456789/14870
Appears in Collections:PhD Thesis of All Public / Private Sector Universities / DAIs.

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