Dual antiplatelet therapy of aspirin and clopidogrel is pivotal for patients undergoing percutaneous coronary intervention. However, the variable platelets reactivity response to clopidogrel may lead to outcome failure and recurrence of cardiovascular events. Although many genetic and nongenetic factors are known, great portion of clopidogrel variable platelets reactivity remain unexplained which challenges the personalization of clopidogrel therapy. Current methods for clopidogrel personalization include CYP2C19 genotyping, pharmacokinetics, and platelets function testing. However, these methods lack precise prediction of clopidogrel outcome, often leading to insufficient prediction. Pharmacometabolomics which is an approach to identify novel biomarkers of drug response or toxicity in biofluids has been investigated to predict drug response. The advantage of pharmacometabolomics is that it does not only predict the response but also provide extensive information on the metabolic pathways implicated with the response. Integrating pharmacogenetics with pharmacometabolomics can give insight on unknown genetic and nongenetic factors associated with the response. This review aimed to review the literature on factors associated with the variable platelets reactivity response to clopidogrel, as well as appraising current methods for the personalization of clopidogrel therapy. We also aimed to review the literature on using pharmacometabolomics approach to predict drug response, as well as discussing the plausibility of using it to predict clopidogrel outcome.

Clopidogrel is a widely-used antiplatelet drug. It is important for the treatment and prevention of coronary heart disease. Clopidogrel can effectively reduce platelet activity and therefore reduce stent thrombosis. However, some patients still have ischemic events despite taking the clopidogrel due to the alteration in clopidogrel metabolism attributable to various genetic and non-genetic factors. This review aims to summarise the mechanisms and causes of clopidogrel resistance (CR) and potential strategies to overcome it. This review summarised the possible effects of genetic polymorphism on CR among the Asian population, especially CYP2C19 *2 / *3 / *17, where the prevalence rate among Asians was 23.00%, 4.61%, 15.18%, respectively. The review also studied the effects of other factors and appropriate strategies used to overcome CR. Generally, CR among the Asian population was estimated at 17.2–81.6%. Therefore, our overview provides valuable insight into the causes of RC. In conclusion, understanding the prevalence of drug metabolism-related genetic polymorphism, especially CYP2C19 alleles, will enhance clinical understanding of racial differences in drug reactions, contributing to the development of personalised medicine in Asia.

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Background:Statins are recommended for cardiovascular protection for people with diabetes (high-risk groups). This study aimed to evaluate the gap between the guidelines of statin utilization and clinical practice among outpatients with type 2 diabetes regarding the patient's age and gender, to assess if this preventive drug is being satisfactorily utilized or not.Materials and Methods:In this cross-sectional study, patients aged <40 or >75 years, pregnant patients, and patients with type 1 diabetes, human immunodeficiency virus, or liver cirrhosis were excluded. Demographics, laboratory parameters, and prevalence of exposure to statin therapy were evaluated. This study was guided by the 2013 American College of Cardiology/American Heart Association cholesterol guidelines. IBM SPSS software was used for data management.Results:The study cohort involved 576 patients, with age being 58.3 ± 8.9 years. There were 50.5% of females and 49.5% of males. Overall 81.1% of patients aged 58.8 ± 8.8 years were statin users and 18.9% of patients aged 56.2 ± 9 years were statin nonusers. About 83.2% of females and 78.9% of males were prescribed statins. Statin medications included simvastatin 79.2%, atorvastatin 11.6%, lovastatin 5.8%, rosuvastatin 2.1%, and pravastatin 1.3%. Statin users’ and nonusers’ adherence was 56.5%, and 41.3% (P = 0.004), respectively. The adherence to medication plan of females and males was 55.7% and 51.6%, respectively (P = 0.004).Conclusion:Patients with diabetes who are at high risk of cardiovascular events, exposure to statin treatment is significantly less than perfect position both in females and males. Nearly one-fifth of the patients with type 2 diabetes are not using statins despite therapeutic necessities.

Neural stem cells are a multipotent population of tissue-specific stem cells with a broad but limited differentiation potential. However, recent studies have shown that over-expression of the pluripotency gene, Oct4, alone is sufficient to initiate a process by which these can form 'induced pluripotent stem cells' (iPS cells) with the same broad potential as embryonic stem cells. This led us to examine the expression of Oct4 in endogenous neural stem cells, as data regarding its expression in neural stem cells in vivo are contradictory and incomplete. In this study we have therefore analysed the expression of Oct4 and other genes associated with pluripotency throughout development of the mouse CNS and in neural stem cells grown in vitro. We find that Oct4 is still expressed in the CNS by E8.5, but that this expression declines rapidly until it is undetectable by E15.5. This decline is coincident with the gradual methylation of the Oct4 promoter and proximal enhancer. Immunostaining suggests that the Oct4 protein is predominantly cytoplasmic in location. We also found that neural stem cells from all ages expressed the pluripotency associated genes, Sox2, c-Myc, Klf4 and Nanog. These data provide an explanation for the varying behaviour of cells from the early neuroepithelium at different stages of development. The expression of these genes also provides an indication of why Oct4 alone is sufficient to induce iPS formation in neural stem cells at later stages.