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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 -
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 -
International Journal of Molecular... Feb 2022Psychopathic traits in youth may lead to adult criminal behaviors/psychopathy. The Val158Met polymorphism of catechol-O-methyltransferase () may influence the risk for...
Psychopathic traits in youth may lead to adult criminal behaviors/psychopathy. The Val158Met polymorphism of catechol-O-methyltransferase () may influence the risk for psychopathy-related behaviors, while acting as a biomarker for predicting treatment response to dopaminergic medications. The literature shows inconsistent findings, making the interpretation of 's role difficult. The aims of this article are (i) to conduct a systematic review to analyze the effects of Val158Met on psychopathic traits in children and adolescents, and (ii) to present new evidence on the developmental trajectory of the association of Val158Met and youth psychopathic traits. For the systematic review, a literature search was conducted using PubMed, EMBASE, OVID Medline and PsychINFO with the search terms for psychopathic traits, Val158Met and age of interest. In our genotype study, the Val158Met genotype of 293 youth with European ancestry was analyzed in association with the psychopathy-related behavior scores from the Child Behavior Checklist and the Psychopathy Screening Device. To examine the potential influence of developmental changes, the sample was split into at or above and below age 13, and analyses were performed in males and females separately. The literature search yielded twenty-eight articles to be included in the systematic review, which demonstrated mixed results on the association depending on environmental factors, sex ratios, age groups and behavioral disorder diagnoses. The results from our genotype study revealed that Met homozygous youth in the below age 13 group and conversely Val carrier youth in the above age 13 group were more likely to display psychopathic traits. To our knowledge, this is the first study to systematically review the effects of Val158Met on psychopathic traits in childhood and adolescence, and to provide new evidence on the changing effects of Val158Met on psychopathy-related behaviors with development. Elucidating the role of the genotype in conjunction with the child versus adolescent stage of development for psychopathic traits may help predict treatment response, and may lead to early intervention and prevention strategies.
Topics: Adolescent; Antisocial Personality Disorder; Catechol O-Methyltransferase; Child; Female; Genetic Predisposition to Disease; Humans; Male; Polymorphism, Single Nucleotide
PubMed: 35163702
DOI: 10.3390/ijms23031782 -
Journal of Clinical Medicine Apr 2022In recent years, antioxidant supplements have become popular to counteract the effects of oxidative stress in fibromyalgia and one of its most distressing symptoms,... (Review)
Review
In recent years, antioxidant supplements have become popular to counteract the effects of oxidative stress in fibromyalgia and one of its most distressing symptoms, pain. The aim of this systematic review was to summarize the effects of antioxidant supplementation on pain levels perceived by patients diagnosed with fibromyalgia. The words used respected the medical search terms related to our objective including antioxidants, fibromyalgia, pain, and supplementation. Seventeen relevant articles were identified within Medline (PubMed), Scopus, Web of Science (WOS), the Cochrane Database of Systematic Review, and the Cochrane Central Register of Controlled Trials. This review found that antioxidant supplementation is efficient in reducing pain in nine of the studies reviewed. Studies with a duration of supplementation of at least 6 weeks showed a benefit on pain perception in 80% of the patients included in these studies. The benefits shown by vitamins and coenzyme Q10 are remarkable. Further research is needed to identify the effects of other types of antioxidants, such as extra virgin olive oil and turmeric. More homogeneous interventions in terms of antioxidant doses administered and duration would allow the effects on pain to be addressed more comprehensively.
PubMed: 35566585
DOI: 10.3390/jcm11092462 -
Pharmaceutics Nov 2022Pharmacogenetics plays a key role in personalized cancer treatment. Currently, the clinically available pharmacogenetic markers for metastatic colorectal cancer (mCRC)... (Review)
Review
Pharmacogenetics plays a key role in personalized cancer treatment. Currently, the clinically available pharmacogenetic markers for metastatic colorectal cancer (mCRC) are in genes related to drug metabolism, such as DPYD for fluoropyrimidines and UGT1A1 for irinotecan. Recently, the impact of host variability in inflammatory and immune-response genes on treatment response has gained considerable attention, opening innovative perspectives for optimizing tailored mCRC therapy. A literature review was performed on the predictive role of immune-related germline genetic biomarkers on pharmacological outcomes in patients with mCRC. Particularly, that for efficacy and toxicity was reported and the potential role for clinical management of patients was discussed. Most of the available data regard therapy effectiveness, while the impact on toxicity remains limited. Several studies focused on the effects of polymorphisms in genes related to antibody-dependent cellular cytotoxicity (FCGR2A, FCGR3A) and yielded promising but inconclusive results on cetuximab efficacy. The remaining published data are sparse and mainly hypothesis-generating but suggest potentially interesting topics for future pharmacogenetic studies, including innovative gene-drug interactions in a clinical context. Besides the tumor immune escape pathway, genetic markers belonging to cytokines/interleukins (IL-8 and its receptors) and angiogenic mediators (IGF1) seem to be the best investigated and hopefully most promising to be translated into clinical practice after validation.
PubMed: 36432658
DOI: 10.3390/pharmaceutics14112468 -
International Journal of Molecular... Mar 2023The term severe mental illness (SMI) encompasses those psychiatric disorders exerting the highest clinical burden and socio-economic impact on the affected individuals... (Review)
Review
The term severe mental illness (SMI) encompasses those psychiatric disorders exerting the highest clinical burden and socio-economic impact on the affected individuals and their communities. Pharmacogenomic (PGx) approaches hold great promise in personalizing treatment selection and clinical outcomes, possibly reducing the burden of SMI. Here, we sought to review the literature in the field, focusing on PGx testing and particularly on pharmacokinetic markers. We performed a systematic review on PUBMED/Medline, Web of Science, and Scopus. The last search was performed on the 17 September 2022, and further augmented with a comprehensive pearl-growing strategy. In total, 1979 records were screened, and after duplicate removal, 587 unique records were screened by at least 2 independent reviewers. Ultimately, forty-two articles were included in the qualitative analysis, eleven randomized controlled trials and thirty-one nonrandomized studies. The observed lack of standardization in PGx tests, population selection, and tested outcomes limit the overall interpretation of the available evidence. A growing body of evidence suggests that PGx testing might be cost-effective in specific settings and may modestly improve clinical outcomes. More efforts need to be directed toward improving PGx standardization, knowledge for all stakeholders, and clinical practice guidelines for screening recommendations.
Topics: Humans; Mental Disorders; Pharmacogenetics
PubMed: 36902205
DOI: 10.3390/ijms24054776 -
Clinical and Translational Science May 2024The clinical application of Pharmacogenomics (PGx) has improved patient safety. However, comprehensive PGx testing has not been widely adopted in clinical practice, and... (Meta-Analysis)
Meta-Analysis Review
The clinical application of Pharmacogenomics (PGx) has improved patient safety. However, comprehensive PGx testing has not been widely adopted in clinical practice, and significant opportunities exist to further optimize PGx in cancer care. This systematic review and meta-analysis aim to evaluate the safety outcomes of reported PGx-guided strategies (Analysis 1) and identify well-studied emerging pharmacogenomic variants that predict severe toxicity and symptom burden (Analysis 2) in patients with cancer. We searched MEDLINE, EMBASE, CENTRAL, clinicaltrials.gov, and International Clinical Trials Registry Platform from inception to January 2023 for clinical trials or comparative studies evaluating PGx strategies or unconfirmed pharmacogenomic variants. The primary outcomes were severe adverse events (SAE; ≥ grade 3) or symptom burden with pain and vomiting as defined by trial protocols and assessed by trial investigators. We calculated pooled overall relative risk (RR) and 95% confidence interval (95%CI) using random effects models. PROSPERO, registration number CRD42023421277. Of 6811 records screened, six studies were included for Analysis 1, 55 studies for Analysis 2. Meta-analysis 1 (five trials, 1892 participants) showed a lower absolute incidence of SAEs with PGx-guided strategies compared to usual therapy, 16.1% versus 34.0% (RR = 0.72, 95%CI 0.57-0.91, p = 0.006, I = 34%). Meta-analyses 2 identified nine medicine(class)-variant pairs of interest across the TYMS, ABCB1, UGT1A1, HLA-DRB1, and OPRM1 genes. Application of PGx significantly reduced rates of SAEs in patients with cancer. Emergent medicine-variant pairs herald further research into the expansion and optimization of PGx to improve systemic anti-cancer and supportive care medicine safety and efficacy.
Topics: Humans; Neoplasms; Pharmacogenetics; Pharmacogenomic Variants; Antineoplastic Agents; Adult; Germ-Line Mutation; Pharmacogenomic Testing; Symptom Burden
PubMed: 38700261
DOI: 10.1111/cts.13781 -
Psychiatry Research Mar 2023Pharmacogenomic (PGx) testing may increase the probability of remission and response in patients with major depressive disorder (MDD) undergoing pharmacotherapy. Given... (Meta-Analysis)
Meta-Analysis
Pharmacogenomic (PGx) testing may increase the probability of remission and response in patients with major depressive disorder (MDD) undergoing pharmacotherapy. Given the potential implications of these outcomes and recent proliferation of PGx studies, we conducted a systematic review to evaluate the effectiveness of PGx testing on clinical outcomes in patients with MDD as compared to treatment as usual (TAU). MEDLINE, Embase, PsycInfo, and CENTRAL were searched for English-language articles from 2000 to 2021 for randomized controlled trials (RCTs) comparing PGx-guided treatment vs. TAU in patients with MDD. Meta-analyses were conducted in R. Ten RCTs were included: eight reported remission and seven reported response. The best available evidence suggests that PGx-guided care for moderate-to-severe adult depression is more likely to result in remission and response than TAU (both risk ratios significant). However, there are limitations in the evidence base, including high risk of bias and inconsistency between trials. Despite the consequent very low certainty in the magnitude of effect, there is confidence in the direction. Though modest, the beneficial effects of PGx for adults with moderate-severe MDD could - as a result of the scope and scale of the condition and its impacts - have important ramifications for patients and the health system.
Topics: Adult; Humans; Antidepressive Agents; Depression; Depressive Disorder, Major; Pharmacogenetics; Treatment Outcome
PubMed: 36780865
DOI: 10.1016/j.psychres.2023.115102 -
Reviews in Medical Virology Sep 2022The aim of this systematic review and network meta-analysis is to evaluate the comparative effectiveness of N95, surgical/medical and non-medical facemasks as personal... (Meta-Analysis)
Meta-Analysis Review
Comparative effectiveness of N95, surgical or medical, and non-medical facemasks in protection against respiratory virus infection: A systematic review and network meta-analysis.
The aim of this systematic review and network meta-analysis is to evaluate the comparative effectiveness of N95, surgical/medical and non-medical facemasks as personal protective equipment against respiratory virus infection. The study incorporated 35 published and unpublished randomized controlled trials and observational studies investigating specific mask effectiveness against influenza virus, SARS-CoV, MERS-CoV and SARS-CoV-2. We searched PubMed, Google Scholar and medRxiv databases for studies published up to 5 February 2021 (PROSPERO registration: CRD42020214729). The primary outcome of interest was the rate of respiratory viral infection. The quality of evidence was estimated using the GRADE approach. High compliance to mask-wearing conferred a significantly better protection (odds ratio [OR], 0.43; 95% confidence interval [CI], 0.23-0.82) than low compliance. N95 or equivalent masks were the most effective in providing protection against coronavirus infections (OR, 0.30; CI, 0.20-0.44) consistently across subgroup analyses of causative viruses and clinical settings. Evidence supporting the use of medical or surgical masks against influenza or coronavirus infections (SARS, MERS and COVID-19) was weak. Our study confirmed that the use of facemasks provides protection against respiratory viral infections in general; however, the effectiveness may vary according to the type of facemask used. Our findings encourage the use of N95 respirators or their equivalents (e.g., P2) for best personal protection in healthcare settings until more evidence on surgical and medical masks is accrued. This study highlights a substantial lack of evidence on the comparative effectiveness of mask types in community settings.
Topics: COVID-19; Humans; Masks; Network Meta-Analysis; Respiratory Tract Infections; SARS-CoV-2
PubMed: 35218279
DOI: 10.1002/rmv.2336