Association of the ACE and AGT gene polymorphisms with global disparities in COVID-19-related deaths.

OBJECTIVE: The aim of the study was to investigate the gene polymorphisms of angiotensin-converting enzyme (ACE), angiotensinogen (AGT), and angiotensin type 1 receptor (AT1R) in association with coronavirus disease 2019 (COVID-19) mortality rates worldwide. METHODS: The prevalence of ACE I/D, AGT M235T, and AT1R A1166C alleles' frequencies in different populations was assessed. Data on COVID-19-related cases and deaths were acquired from the European Center for Disease Prevention and Control, which included weekly reports by country and continent. An Excel tool was developed to visualize the acquired data of mortality and incidence by classifying them by continent/country across specific periods of time. Spearman's nonparametric correlation was used to evaluate the association between country-based frequencies in RAS gene polymorphisms and COVID-19-related deaths. RESULTS: While China constituted the initial reservoir of COVID-19, incidence/mortality rates in Europe and America outnumbered the figures in the former. A clear association was identified between death rates and ACE D/I ( r = 0.3659; P = 0.033), as well as AGT A/G variants ( r = 0.7576; P = 0.015). Data on AT1R polymorphisms suggested no correlation with mortality rates. CONCLUSION: Our results demonstrated a significant disparity in COVID-19-related susceptibility and mortality among different populations and corroborate the importance of gene polymorphisms in predicting and consequently improving patients' outcomes.

Optimizing clopidogrel dose response: a new clinical algorithm comprising CYP2C19 pharmacogenetics and drug interactions.

PURPOSE: Response to clopidogrel varies widely with nonresponse rates ranging from 4% to 30%. A reduced function of the gene variant of the CYP2C19 has been associated with lower drug metabolite levels, and hence diminished platelet inhibition. Drugs that alter CYP2C19 activity may also mimic genetic variants. The aim of the study is to investigate the cumulative effect of CYP2C19 gene polymorphisms and drug interactions that affects clopidogrel dosing, and apply it into a new clinical-pharmacogenetic algorithm that can be used by clinicians in optimizing clopidogrel-based treatment. METHOD: Clopidogrel dose optimization was analyzed based on two main parameters that affect clopidogrel metabolite area under the curve: different CYP2C19 genotypes and concomitant drug intake. Clopidogrel adjusted dose was computed based on area under the curve ratios for different CYP2C19 genotypes when a drug interacting with CYP2C19 is added to clopidogrel treatment. A clinical-pharmacogenetic algorithm was developed based on whether clopidogrel shows 1) expected effect as per indication, 2) little or no effect, or 3) clinical features that patients experience and fit with clopidogrel adverse drug reactions. RESULTS: The study results show that all patients under clopidogrel treatment, whose genotypes are different from *1*1, and concomitantly taking other drugs metabolized by CYP2C19 require clopidogrel dose adjustment. To get a therapeutic effect and avoid adverse drug reactions, therapeutic dose of 75 mg clopidogrel, for example, should be lowered to 6 mg or increased to 215 mg in patients with different genotypes. CONCLUSION: The implementation of clopidogrel new algorithm has the potential to maximize the benefit of clopidogrel pharmacological therapy. Clinicians would be able to personalize treatment to enhance efficacy and limit toxicity.

Renin-angiotensin-system gene polymorphisms and depression.

Given the abundance of the renin-angiotensin system (RAS) components in the brain, their importance in behavior and cognition, and the data that implicates them in the etiology and treatment of depression, it is possible that those RAS gene polymorphisms associated with increased RAS activity may also be associated with depression. The frequencies of common polymorphisms of genes encoding for components of the RAS, namely angiotensinogen (M235T), angiotensin converting enzyme (ACE) (insertion, I; deletion, D), angiotensin receptor type I (A1166C), and angiotensin receptor type II (C3123A) were determined in DNA extracted from buccal cells from a Lebanese population of 132 depressed patients and their first-degree relative case-controls. The angiotensin receptor type 1 (A1166C) CC genotype was significantly associated with depression (p=0.036). None of the other common RAS-associated polymorphisms were significantly associated. The results support the hypothesis that increased RAS activity may increase relative risk of depression in that the angiotensin receptor type 1 (A1166C) CC genotype is associated with increased responsiveness to angiotensin II.

Buccal cell DNA extraction: yield, purity, and cost: a comparison of two methods.

Simple and cost-effective methods are needed to extract DNA in order to use it in large-scale studies. Blood is an excellent DNA source; however, it is costly and invasive thus an alternative is needed. Several kits and chemical protocols using buccal cells have been proposed for DNA extraction. The objective of the study is to evaluate buccal NaOH chemical protocol and Nucleospin Tissue Kit (BD Biosciences, Macery-Nagel, Germany) for DNA extraction. DNA swab samples were collected from 300 voluntary participants. DNA yields and purity were measured by NaOH and Nucleospin Tissue Kit techniques; the cost and time consumption for DNA extraction per sample were assessed as well. Results have shown that DNA amount and purity extracted by NaOH procedure was compared to that of the kit (p = 0.164; p = 0.249, respectively). NaOH method was considered cheaper and less time consuming (0.06 versus 3.80 USD, and 1.33 versus 3.59 minutes per sample, p < 0.001). Buccal cell derived DNA extracted by NaOH protocol can be considered a feasible substitute for more expensive and time-consuming kits.

Inappropriate medication use in elderly lebanese outpatients: prevalence and risk factors.

BACKGROUND: Inappropriate use of medications has become an international cause for concern in geriatric patients, who are at high risk of drug-related morbidity. This study is the first attempt to determine the prevalence of inappropriate drug use in elderly Lebanese outpatients, using community pharmacy data, and to identify factors that predict potentially inappropriate drug intake in this population. METHODS: Records of elderly patients aged > or =65 years were selected from different community pharmacies. Each patient profile was reviewed and to confirm patient record information, in-person interviews were conducted with elderly patients between November 2004 and May 2005 by qualified pharmacists. Based on a literature review describing guidelines for the inappropriate use of medications in the elderly, courses of therapy were assessed and classified as either appropriate or inappropriate. Courses of therapy that were judged inappropriate were further classified according to the specific area of inappropriate use (i.e. Beers' criteria, duplicate therapy, indication, dose, dose frequency including missing doses, duration and discontinuation of therapy, adverse effects, drug-drug and/or drug-disease interactions, and poor memory). Statistical analyses were performed to estimate the prevalence of inappropriate medication use and to identify potentially predictive factors of such use arising from patients' sociodemographic characteristics, health factors and drug regimen intake. RESULTS: A total of 350 elderly patient profiles were reviewed, from which 277 evaluable records were obtained. More than half (59.6%) of the patients taking drugs at the time of the study were taking at least one inappropriate medication. Inappropriate medication use was most frequently identified in terms of Beers' criteria (22.4%), missing doses (18.8%) or incorrect frequency of administration of drugs (13.0%). Factors predicting potentially inappropriate drug intake included female sex (65.7% vs 53.3% for males, p = 0.03) and alcohol intake (p = 0.007). There were also significant associations between the likelihood of use of an inappropriate drug and (i) increased number of medical illnesses (p < 0.00002); and (ii) consumption of an over-the-counter drug (OTC) and/or prescription drug (p = 0.048 and p = 0.0035, respectively). The likelihood of use of an inappropriate drug was higher again when patients concurrently used both OTC and prescription drugs (p < 0.0002). CONCLUSION: The present study is the first to describe and assess inappropriate medication use by elderly outpatients in the Lebanese community setting. With increasing availability of newer and more appropriate medications, use of potentially inappropriate drugs may decrease. Pharmacists have a major role to play in counselling patients about the importance of appropriate drug use.