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Neuropsychiatric Disease and Treatment 2021Evidence supporting the utility of pharmacogenetic (PGX) tests in depression is scarce. The main objectives of this study were to summarize, update, and assess the... (Review)
Review
OBJECTIVE
Evidence supporting the utility of pharmacogenetic (PGX) tests in depression is scarce. The main objectives of this study were to summarize, update, and assess the quality of the available evidence regarding PGX testing in depression as well as estimating the impact of using PGX testing tools in depression outcomes in the Middle East/North Africa (MENA) region.
METHODOLOGY
Scientific databases were systematically searched from inception to June 30, 2020 for systematic reviews and randomized controlled trials (RCTs) assessing the clinical utility of PGX tests in the treatment of depression. Meta-analyses only and RCTs that were included in eligible systematic reviews were excluded. The quality of the eligible studies was assessed using the Crowe Critical Appraisal Tool (CCAT).
RESULTS
Six systematic reviews and three RCTs met the inclusion criteria and were included in this study. The results of the systematic reviews provided weak evidence on the efficacy of PGX testing, especially in patients with moderate-severe depression at 8 weeks. In addition, there was a lack of evidence regarding safety outcomes. Newer RCTs with better quality showed clinical promise regarding efficacy outcomes, especially in patients with gene-drug interactions. No evidence was found regarding PGX testing impact in the MENA region.
CONCLUSION
This systematic review is an update and summary of the available literature on the clinical utility of PGX testing in depression. The findings of this study demonstrate that PGX testing prior to treatment initiation or during the course of therapy may improve efficacy outcomes. Further studies are warranted to assess the impact of PGX testing on safety outcomes.
PubMed: 34321882
DOI: 10.2147/NDT.S312966 -
The Pharmacogenomics Journal Dec 2022The successful implementation of pharmacogenetics (PGx) into clinical practice requires patient genomic data to be shared between stakeholders in multiple settings. This...
The successful implementation of pharmacogenetics (PGx) into clinical practice requires patient genomic data to be shared between stakeholders in multiple settings. This creates a number of barriers to widespread adoption of PGx, including privacy concerns related to the storage and movement of identifiable genomic data. Informatic solutions that support secure and equitable data access for genomic data are therefore important to PGx. Here we propose a methodology that uses smart contracts implemented on a blockchain-based framework, PGxChain, to address this issue. The design requirements for PGxChain were identified through a systematic literature review, identifying technical challenges and barriers impeding the clinical implementation of pharmacogenomics. These requirements included security and privacy, accessibility, interoperability, traceability and legal compliance. A proof-of-concept implementation based on Ethereum was then developed that met the design requirements. PGxChain's performance was examined using Hyperledger Caliper for latency, throughput, and transaction success rate. The findings clearly indicate that blockchain technology offers considerable potential to advance pharmacogenetic data sharing, particularly with regard to PGx data security and privacy, large-scale accessibility of PGx data, PGx data interoperability between multiple health care providers and compliance with data-sharing laws and regulations.
Topics: Humans; Blockchain; Pharmacogenetics; Computer Security; Information Dissemination; Pharmacogenomic Testing
PubMed: 35869255
DOI: 10.1038/s41397-022-00285-5 -
Pharmacology Research & Perspectives Dec 2023Pharmacogenomics remains underutilized in clinical practice, despite the existence of internationally recognized, evidence-based guidelines. This systematic review aims... (Review)
Review
Pharmacogenomics remains underutilized in clinical practice, despite the existence of internationally recognized, evidence-based guidelines. This systematic review aims to understand enablers and barriers to pharmacogenomics implementation in pediatric oncology by assessing the knowledge, attitudes, and practice of healthcare professionals and consumers. Medline, Embase, Emcare, and PsycINFO database searches identified 146 relevant studies of which only three met the inclusion criteria. These studies reveal that consumers were concerned with pharmacogenomic test costs, insurance discrimination, data sharing, and privacy. Healthcare professionals possessed mostly positive attitudes toward pharmacogenomic testing yet identified lack of experience and training as barriers to implementation. Education emerged as the key enabler, reported in all three studies and both healthcare professionals and consumer groups. However, despite the need for education, no studies utilizing a pediatric oncology consumer or healthcare professional group have reported on the implementation or analysis of a pharmacogenomic education program in pediatric oncology. Increased access to guidelines, expert collaborations and additional guidance interpreting results were further enablers established by healthcare professionals. The themes identified mirror those reported in broader pediatric genetic testing literature. As only a small number of studies met inclusion criteria for this review, further research is warranted to elicit implementation determinants and advance pediatric pharmacogenomics.
Topics: Humans; Child; Pharmacogenetics; Health Knowledge, Attitudes, Practice; Health Personnel; Medical Oncology; Neoplasms
PubMed: 38013228
DOI: 10.1002/prp2.1150 -
Tidsskrift For Den Norske Laegeforening... Nov 2017Population groups of different ancestry appear to have varying prevalence of diabetes, different risks of developing cardiovascular disease and different responses to... (Review)
Review
BACKGROUND
Population groups of different ancestry appear to have varying prevalence of diabetes, different risks of developing cardiovascular disease and different responses to certain drugs that are used for these conditions. We wished to review the literature in this field.
MATERIAL AND METHOD
We have performed searches in several databases for systematic review articles published from the year 2000 onwards, and supplemented these with articles from reference lists, our own literature archives and a pyramid search in the Norwegian Electronic Health Library database. Altogether 37 articles were included.
RESULTS
With regard to diagnosed diabetes, the prevalence of coronary heart disease and stroke varies among groups of South Asian, East Asian, African and European ancestry. In patients of South Asian ancestry, the risk of coronary heart disease appears to be twice that of Europeans, and the disease occurs 5–10 years earlier. The prevalence of stroke is especially high in persons of African ancestry. Risk factors such as dyslipidemia and hypertension are distributed differently among these groups. The therapeutic response to drugs such as beta blockers, ACE inhibitors and various statins differs; for example, statin doses in Asians may often be halved in relation to those used for Caucasians, and ACE inhibitors are not recommended as monotherapy for hypertension in persons of African ancestry. These differences are partly attributable to variations in genetic disposition.
INTERPRETATION
The findings are clinically significant – better insight in this field enables optimal tailoring of treatment for each patient, with more rapid achievement of goals and reduced risk of adverse effects. The recommendations given in this article are consistent with and complement the Directorate of Health’s revised guidelines for the treatment of diabetes.
Topics: Antihypertensive Agents; Asian People; Black People; Cardiovascular Diseases; Diabetes Mellitus; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Pharmacogenetics; Stroke; White People
PubMed: 29181932
DOI: 10.4045/tidsskr.16.0680 -
British Journal of Clinical Pharmacology Oct 2015Adverse drug events lead to increased morbidity, mortality and health care costs. Pharmacogenetic testing that guides drug prescribing has the potential to reduced... (Meta-Analysis)
Meta-Analysis Review
AIM
Adverse drug events lead to increased morbidity, mortality and health care costs. Pharmacogenetic testing that guides drug prescribing has the potential to reduced adverse drug events and increase drug effectiveness. Our aim was to quantify the clinical effectiveness of genotype-guided prescribing.
METHODS
Three electronic databases were searched from January 1980 through December 2013. Studies were eligible if they were RCTs comparing genotype-guided prescribing with non-genetic informed prescribing, reported drug specific adverse drug events and clinical effectiveness outcomes. Two reviewers independently screened titles and abstracts, extracted data and assessed study quality. Meta-analyses of specific outcomes were conducted where data allowed.
RESULTS
Fifteen studies, involving 5688 patients and 19 drugs, met the inclusion and exclusion criteria. Eight studies had statistically significant results for their primary outcome in favour of genotype-guided prescribing. Nine studies evaluated genotype-guided warfarin dosing. Analysis of percentage of time in therapeutic international normalized ratio range (1952 individuals) showed a statistically significant benefit in favour of genotype-guided warfarin dosing (mean difference = 6.67; 95% CI 1.34, 12.0, I(2) = 80%). There was a statistically significant reduction in numbers of warfarin-related minor bleeding, major bleeding and thromboembolisms associated with genotype guided warfarin dosing, relative risk 0.57 (95% CI 0.33, 0.99; I(2) = 60%). It was not possible to meta-analyze genotype-guided dosing for other drugs. Of the six non-warfarin genotype-guided trials, two demonstrated a statistically significant benefit for their primary outcome, odds ratio 0.03 (95% CI 0.00, 0.62, P < 0.001) for abacavir.
CONCLUSIONS
There is evidence of improved clinical effectiveness associated with genotype-guided warfarin dosing.
Topics: Drug Prescriptions; Drug-Related Side Effects and Adverse Reactions; Genotype; Humans; Pharmacogenetics; Randomized Controlled Trials as Topic
PubMed: 25060532
DOI: 10.1111/bcp.12475 -
Biomedicines Nov 2021Inflammatory Bowel Disease (IBD) comprises a group of disorders, in particular Crohn's disease (CD) and ulcerative colitis (UC), characterized by chronic inflammation... (Review)
Review
Inflammatory Bowel Disease (IBD) comprises a group of disorders, in particular Crohn's disease (CD) and ulcerative colitis (UC), characterized by chronic inflammation affecting the gastrointestinal tract. The treatment of these conditions is primarily based on anti-inflammatory drugs, although the use of biological drugs with lower side effects quickly increased in the last decade. However, the presence of certain polymorphisms in the population may determine a different outcome in response to therapy, reflecting the heterogeneity of the efficacy in patients. Considering that several studies showed important correlations between genetic polymorphisms and response to biological treatments in IBD patients, this systematic review aims to summarize the pharmacogenetics of biologicals approved for IBD, thus highlighting a possible association between some polymorphisms and drug response. With this purpose, we reviewed PubMed papers published over the past 21 years (2000-2021), using as the search term "drug name and IBD or CD or UC and polymorphisms" to underline the role of pharmacogenetic tests in approaching the disease with a targeted therapy.
PubMed: 34944563
DOI: 10.3390/biomedicines9121748 -
Arquivos de Neuro-psiquiatria Jan 2023Pharmacogenetics promises better control of diseases such as cardiovascular disease (CVD). Acetylsalicylic acid, aspirin, prevents the formation of an activating agent...
BACKGROUND
Pharmacogenetics promises better control of diseases such as cardiovascular disease (CVD). Acetylsalicylic acid, aspirin, prevents the formation of an activating agent of platelet aggregation and vasoconstriction, and it is used to prevent CVD. Nevertheless, patients may have treatment failure due to genetic variants that modify the metabolism of the drug causing aspirin resistance (AR).
OBJECTIVES
To realize a systematic literature review to determine the impact of genetic variants on AR.
METHODS
Articles published in the MEDLINE/PubMed, Cochrane, Scopus, LILACS, and SCIELO databases were systematically screened. A total of 290 articles were identified and 269 articles were excluded because they did not comply with the previously established inclusion criteria. A total of 20 case-control studies and 1 cohort was included.
RESULTS
The genetic variants rs1126643 (), rs3842787 (), rs20417 (), and rs5918 () were the most studied. As for relevance, of the 64 genetic variants evaluated by the articles, 14 had statistical significance ( < 0.05; 95% confidence interval [CI]) in at least one article. Among them, the following have had unanimous results: rs1371097 (), rs1045642 (), rs1051931 and rs7756935 (), rs2071746 (), rs1131882 and rs4523 (), rs434473 (), rs9315042 (), and rs662 (), while these differ in real interference in AR: rs5918 (), rs2243093 (), rs1330344 (), and rs20417 (). As study limitations, we highlight the nonuniform methodologies of the analyzed articles and population differences.
CONCLUSION
It is noteworthy that pharmacogenetics is an expanding area. Therefore, further studies are needed to better understand the association between genetic variants and AR.
Topics: Humans; Aspirin; Cardiovascular Diseases; Cyclooxygenase 2; Pharmacogenetics; Platelet Aggregation Inhibitors; Drug Resistance
PubMed: 36918009
DOI: 10.1055/s-0042-1758445 -
Oncotarget Feb 2017Recent development of cutting edge research found that long noncoding RNAs (lncRNAs) plays important roles in carcinogenesis and progression. In Southeast Asia and North... (Review)
Review
Recent development of cutting edge research found that long noncoding RNAs (lncRNAs) plays important roles in carcinogenesis and progression. In Southeast Asia and North Africa, nasopharyngeal carcinoma (NPC) is the most common aggressive squamous cell carcinoma. Nasopharyngeal carcinoma is most frequently occurring in males. However, nasopharyngeal carcinoma is caused by a combination of several factors as viral, environmental factors, and heredity. Till now, the potential pathway or mechanism of NPC is not well known. In our present review, we strongly emphasized on long noncoding RNAs (lncRNAs) and its significant role in nasopharyngeal carcinoma. It has been showed that lncRNAs regulate the development and progression of different types of cancers, including NPC. In addition, it has been found that chromatin organization, transcriptional and post-transcriptional events are regulated by lncRNAs. Our present review summarizes the roles of lncRNAs in nasopharyngeal carcinoma and provides an overview of the feasibility of lncRNAs as diagnosis, prognosis and potential treatment for NPC patients.
Topics: Humans; Carcinogenesis; Carcinoma; Cell Line, Tumor; Disease Progression; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Prognosis; RNA, Long Noncoding
PubMed: 28039476
DOI: 10.18632/oncotarget.14211 -
Genetics Research 2023Pharmacogenetics is a potential approach that can be applied to decline the burden of rivaroxaban's ADRs. The current systematic review and meta-analysis aim to identify... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Pharmacogenetics is a potential approach that can be applied to decline the burden of rivaroxaban's ADRs. The current systematic review and meta-analysis aim to identify genetic variants correlated with rivaroxaban exposure and evaluate their importance.
METHODS
We systematically searched PubMed, Web of Science, and Scopus databases for all observational and interventional studies. The fixed effect method was used to pool the data when the Q-test's value was higher than 0.1. We used random models when the value was less than 0.1.
RESULTS
Data from ten studies (4721 participants) were analyzed in the current review. Qualitative synthesis from included studies found that two variants of ABCB1 (rs1045642 and rs2032582) and one variant of APOB (rs13306198) are potential contributors to rivaroxaban concentrations. Both wild homozygotes (AA) and heterozygotes (AC) of rs1045642 have significantly lower rivaroxaban concentrations compared to mutated homozygotes (CC) (SMD = 0.516, 95% CI: 0.115 to 0.917; SMD = 0.772, 95% CI: 0.088 to 1.455, respectively). Nevertheless, pooling unadjusted odds ratios did not yield a statistically significant correlation between rivaroxaban ADRs and genetic mutations.
CONCLUSION
This study revealed that being an AC or CC for rs1045642 is attributed to a considerably higher rivaroxaban level in participants using rivaroxaban. That is to say, rs1045642 is a remarkable predictor of rivaroxaban metabolism. We concluded that identifying rs1045642 before drug administration might decrease ADRs although further studies adjusted for potential confounders are strongly suggested.
Topics: Humans; Rivaroxaban; Pharmacogenetics; Homozygote; Heterozygote; Drug-Related Side Effects and Adverse Reactions
PubMed: 37942082
DOI: 10.1155/2023/6105320 -
Addiction Science & Clinical Practice Nov 2021Patients with opioid use disorder (OUD) display an interindividual variability in their response to medications for opioid use disorder (MOUD). A genetic basis may... (Review)
Review
BACKGROUND
Patients with opioid use disorder (OUD) display an interindividual variability in their response to medications for opioid use disorder (MOUD). A genetic basis may explain the variability in this response. However, no consensus has been reached regarding which genetic variants significantly contribute to MOUD outcomes.
OBJECTIVES
This systematic review aims to summarize genome-wide significant findings on MOUD outcomes and critically appraise the quality of the studies involved.
METHODS
Databases searched from inception until August 21st, 2020 include: MEDLINE, Web of Science, EMBASE, CINAHL and Pre-CINAHL, GWAS Catalog and GWAS Central. The included studies had to be GWASs that assessed MOUD in an OUD population. All studies were screened in duplicate. The quality of the included studies was scored and assessed using the Q-Genie tool. Quantitative analysis, as planned in the protocol, was not feasible, so the studies were analyzed qualitatively.
RESULTS
Our search identified 7292 studies. Five studies meeting the eligibility criteria were included. However, only three studies reported results that met our significance threshold of p ≤ 1.0 × 10. In total, 43 genetic variants were identified. Variants corresponding to CNIH3 were reported to be associated with daily heroin injection in Europeans, OPRM1, TRIB2, and ZNF146 with methadone dose in African Americans, EYS with methadone dose in Europeans, and SPON1 and intergenic regions in chromosomes 9 and 3 with plasma concentrations of S-methadone, R-methadone, and R-EDDP, respectively, in Han Chinese.
LIMITATIONS
The limitations of this study include not being able to synthesize the data in a quantitative way and a conservative eligibility and data collection model.
CONCLUSION
The results from this systematic review will aid in highlighting significant genetic variants that can be replicated in future OUD pharmacogenetics research to ascertain their role in patient-specific MOUD outcomes. Systematic review registration number CRD42020169121.
Topics: Buprenorphine; Calcium-Calmodulin-Dependent Protein Kinases; Eye Proteins; Genome-Wide Association Study; Humans; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders; Polymorphism, Single Nucleotide
PubMed: 34838141
DOI: 10.1186/s13722-021-00278-y