Genes (Basel). 2022 Aug 5;13(8):1394. doi: 10.3390/genes13081394.

ABSTRACT

OBJECTIVE: This study describes the single nucleotide polymorphisms (SNPs) in amlodipine-associated genes and assesses their correlation with blood pressure control among South African adults with hypertension.

METHODS: In total, 304 hypertensive patients on amlodipine treatment belonging to the indigenous Swati, Xhosa and Zulu population groups of South Africa were recruited between June 2017 and June 2019. Participants were categorized into: controlled (blood pressure < 140/90 mmHg) and uncontrolled (blood pressure ≥ 140/90 mmHg) hypertension. Thirteen SNPs in amlodipine pharmacogenes with a high PharmGKB evidence base were selected and genotyped using MassArray (Agena BioscienceTM). Logistic regression was fitted to identify significant associations between the SNPs and blood pressure control with amlodipine.

RESULTS: The majority of the participants were females (76.6%), older than 45 years (89.1%) and had uncontrolled hypertension (52.3%). Of the 13 SNPs genotyped, five SNPs, rs1042713 (minor allele frequency = 45.9%), rs10494366 (minor allele frequency = 35.3%), rs2239050 (minor allele frequency = 28.7%), rs2246709 (minor allele frequency = 51.6%) and rs4291 (minor allele frequency = 34.4%), were detected among the Xhosa participants, while none were detected among the Swati and Zulu tribal groups. Variants rs1042713 and rs10494366 demonstrated an expression frequency of 97.5% and 79.5%, respectively. Variant TA genotype of rs4291 was significantly associated with uncontrolled hypertension. No association was established between blood pressure response to amlodipine and the remaining four SNPs.

CONCLUSIONS: This study reports the discovery of five SNPs in amlodipine genes (rs2239050, rs2246709, rs4291, rs1042713 and rs10494366) among the indigenous Xhosa-speaking tribe of South Africa. In addition, the TA genotype of rs4291 was associated with blood pressure control in this cohort. These findings might open doors for more pharmacogenomic studies, which could inform innovations to personalised anti-hypertensive treatment in the ethnically diverse population of South Africa.

PMID:36011305 | DOI:10.3390/genes13081394

Cancers (Basel). 2022 Aug 14;14(16):3922. doi: 10.3390/cancers14163922.

ABSTRACT

Despite the fact that the incidence of gastric cancer has declined over the last decade, it is still the world's leading cause of cancer-related death. The diagnosis of early gastric cancer is difficult, as symptoms of this cancer only manifest at a late stage of cancer progression. Thus, the prognosis of gastric cancer is poor, and the current treatment for improving patients' outcomes involves the application of surgery and chemotherapy. Immunotherapy is one of the most recent therapies for gastric cancer, whereby the immune system of the host is programmed to combat cancer cells, and the therapy differs based upon the patient's immune system. However, an understanding of the role of immune cells, namely the cell-mediated immune response and the humoral immune response, is pertinent for applications of immunotherapy. The roles of immune cells in the prognosis of gastric cancer have yielded conflicting results. This review discusses the roles of immune cells in gastric cancer pathogenesis, specifically, T cells, B cells, macrophages, natural killer cells, and dendritic cells, as well as the evidence presented thus far. Understanding how cancer cells interact with immune cells is of paramount importance in designing treatment options for gastric cancer immunotherapy.

PMID:36010915 | DOI:10.3390/cancers14163922

Cells. 2022 Aug 19;11(16):2586. doi: 10.3390/cells11162586.

ABSTRACT

Despite the general awareness of the need to reduce air pollution, the efforts were undertaken in Poland to eliminate the pollutants and their harmful effect on human health seem to be insufficient. Moreover, the latest data indicate that the city of Krakow is at the forefront of the most polluted cities worldwide. Hence, in this report, we investigated the impact of particulate matter isolated from the air of Krakow (PM KRK) on the gene expression profile of peripheral blood mononuclear cells (PBMCs) in healthy donors (HD) and patients with atherosclerosis (AS), rheumatoid arthritis (RA) and multiple sclerosis (MS), after in vitro exposure. Blood samples were collected in two seasons, differing in the concentration of PM in the air (below or above a daily limit of 50 µg/m3 for PM 10). Data show that PBMCs exposed in vitro to PM KRK upregulated the expression of genes involved, among others, in pro-inflammatory response, cell motility, and regulation of cell metabolism. The transcriptional effects were observed predominantly in the group of patients with AS and MS. The observed changes seem to be dependent on the seasonal concentration of PM in the air of Krakow and may suggest their important role in the progression of AS, MS, and RA in the residents of Krakow.

PMID:36010662 | DOI:10.3390/cells11162586

Diagnostics (Basel). 2022 Aug 22;12(8):2025. doi: 10.3390/diagnostics12082025.

ABSTRACT

Preterm premature rupture of the membranes (PPROM) at the limit of viability is associated with low neonatal survival rates and a high rate of neonatal complications in survivors. It carries a major risk of maternal morbidity and mortality. The limit of viability can be defined as the earliest stage of fetal maturity when a fetus has a reasonable chance, although not a high likelihood, for extra-uterine survival. The study reviews available data on preventing preterm delivery caused by the previable PPROM, pregnancy latency, therapeutic options including the use of antibiotics and steroids, neonatal outcomes, and future directions and opportunities.

PMID:36010375 | DOI:10.3390/diagnostics12082025

Antioxidants (Basel). 2022 Aug 19;11(8):1609. doi: 10.3390/antiox11081609.

ABSTRACT

The coronavirus disease (COVID-19) pandemic is a leading global health and economic challenge. What defines the disease's progression is not entirely understood, but there are strong indications that oxidative stress and the defense against reactive oxygen species are crucial players. A big influx of immune cells to the site of infection is marked by the increase in reactive oxygen and nitrogen species. Our article aims to highlight the critical role of oxidative stress in the emergence and severity of COVID-19 and, more importantly, to shed light on the underlying molecular and genetic mechanisms. We have reviewed the available literature and clinical trials to extract the relevant genetic variants within the oxidative stress pathway associated with COVID-19 and the anti-oxidative therapies currently evaluated in the clinical trials for COVID-19 treatment, in particular clinical trials on glutathione and N-acetylcysteine.

PMID:36009328 | DOI:10.3390/antiox11081609

Antioxidants (Basel). 2022 Aug 19;11(8):1602. doi: 10.3390/antiox11081602.

ABSTRACT

Repetitive seizures, a common phenomenon in diverse neurologic conditions such as epilepsy, can undoubtedly cause neuronal injury and our prior work reveals that ferroptosis is a contributing factor of neuronal damage post seizure. However, there is no drug available in clinical practice for ameliorating seizure-induced neuronal impairment via targeting ferroptosis. Our present work aimed to explore whether D-penicillamine (DPA), an originally approved drug for treating Wilson's disease, inhibited neuronal ferroptosis and alleviated seizure-associated brain damage. Our findings revealed that DPA remarkably improved neuronal survival in kainic acid (KA)-treated mouse model. Furthermore, ferroptosis-associated indices including acyl-coA synthetase long chain family member 4 (ACSL4), prostaglandin-endoperoxide synthase 2 (Ptgs2) gene and lipid peroxide (LPO) level were significantly decreased in KA mouse model after DPA treatment. In a ferroptotic cell death model induced by glutamate or erastin, DPA was also validated to evidently suppress neuronal ferroptosis. The results from RNA-seq analysis indicated that Aqp11, a gene coding previously reported channel protein responsible for transporting water and small solutes, was identified as a molecular target by which DPA exerted anti-ferroptotic potential in neurons. The experimental results from in vivo Aqp11 siRNA transfer into the brain also confirmed that knockdown of Aqp11 abrogated the inhibitory effect of seizure-induced ferroptosis after DPA treatment, suggesting that the effects of DPA on ferroptosis process are dependent upon Aqp11. In conclusion, DPA can be repurposed to cure seizure disorders such as epilepsy.

PMID:36009321 | DOI:10.3390/antiox11081602

Trends Pharmacol Sci. 2022 Aug 22:S0165-6147(22)00171-7. doi: 10.1016/j.tips.2022.07.002. Online ahead of print.

ABSTRACT

Recent advances in next-generation sequencing (NGS) have resulted in the identification of tens of thousands of rare pharmacogenetic variations with unknown functional effects. However, although such pharmacogenetic variations have been estimated to account for a considerable amount of the heritable variability in drug response and toxicity, accurate interpretation at the level of the individual patient remains challenging. We discuss emerging strategies and concepts to close this translational gap. We illustrate how massively parallel experimental assays, artificial intelligence (AI), and machine learning can synergize with population-scale biobank projects to facilitate the interpretation of NGS data to individualize clinical decision-making and personalized medicine.

PMID:36008164 | DOI:10.1016/j.tips.2022.07.002

Prog Mol Biol Transl Sci. 2022;190(1):147-188. doi: 10.1016/bs.pmbts.2022.04.001. Epub 2022 May 23.

ABSTRACT

Epilepsy is a common neurological disorder affecting over 50 million people worldwide. Although more than 20 new anti-seizure medications have been developed in the past three decades, about one-third of patients still experience recurrent seizures. The heterogeneity of epilepsy types and the highly variable inter-individual response to the therapies makes disease management challenging. A precision medicine approach of treatment for epilepsy patients that considers individual patient characteristics has long been advocated. With advances in DNA sequencing technology, it has been estimated than >30% of all epilepsy syndromes have genetic components. Here we summarize recent approaches in genetic testing and current personalized treatments that are already applicable in genetic epilepsy syndromes. We also discuss current precision therapy utilized in personalized pharmacogenomics, as well as tailored treatment with neuromodulation for epilepsy patients. In the near future, we envision precision medicine in epilepsy will be applicable on a large scale involving not only targeted therapies, but also diagnosis, prognosis, and comorbidity management.

PMID:36007998 | DOI:10.1016/bs.pmbts.2022.04.001

Aging (Albany NY). 2022 Aug 24;14(undefined). doi: 10.18632/aging.204244. Online ahead of print.

ABSTRACT

BACKGROUND: Recent studies identified correlations between splicing factors (SFs) and tumor progression and therapy. However, the potential roles of SFs in immune regulation and the tumor microenvironment (TME) remain unknown.

METHODS: We used UpSet plots to screen for prognostic-related alternative splicing (AS) events. We evaluated SF patterns in specific immune landscapes. Single sample gene set enrichment analysis (ssGSEA) algorithms were used to quantify relative infiltration levels in immune cell subsets. Principal component analysis (PCA) algorithm-based SFscore were used to evaluate SF patterns in individual tumors with an immune response.

RESULTS: From prognosis-related AS events, 16 prognosis-related SFs were selected to construct three SF patterns. Further TME analyses showed these patterns were highly consistent with immune-inflamed, immune-excluded, and immune-desert landscapes. Based on SFscore constructed using differentially expressed genes (DEGs) between SF patterns, patients were classified into two immune-subtypes associated with differential pharmacogenomic landscapes and cell features. A low SFscore was associated with high immune cell infiltration, high tumor mutation burden (TMB), and elevated expression of immune check points (ICPs), indicating a better immune response.

CONCLUSIONS: SFs are significantly associated with TME remodeling. Evaluating different SF patterns enhances our understanding of the TME and improves effective immunotherapy strategies.

PMID:36006412 | DOI:10.18632/aging.204244

Pharmacy (Basel). 2022 Aug 5;10(4):95. doi: 10.3390/pharmacy10040095.

ABSTRACT

Currently, metastatic colon cancer is treated with monotherapeutic regimens such as folinic acid, fluorouracil, and oxaliplatin (FOLFOX), capecitabine and oxaliplatin (CapeOX), and leucovorin, fluorouracil, and irinotecan hydrochloride (FOLFIRI). Other treatments include biological therapies and immunotherapy with drugs such as bevacizumab, panitumumab, cetuximab, and pembrolizumab. After the research, it was found that some mutations make those treatments not as effective in all patients. In this bibliographic review, we investigated the pharmacogenetic explanations for how mutations in the genes coding for rat sarcoma virus (RAS) and rapidly accelerated fibrosarcoma (RAF) reduce the effectiveness of these treatments and allow the continued proliferation of tumors. Furthermore, we note that patients with mutations in the dihydropyrimidine dehydrogenase (DPDY) gene usually require lower doses of therapies such as 5-fluorouracyl (5-FU) and capecitabine to avoid severe adverse effects. Some other mutations in the thymidylate synthase gene (TSYM), methylenetetrahydrofolate reductase gene (MTHFR), and ATP binding cassette transporter B (ABCB1 and ABCB2) affect efficacy and security of the treatments. It is important to address the clinical implication of the oncologist in the study of gene mutations than can influence in the antitumoral response and safety of colon cancer treatments.

PMID:36005935 | DOI:10.3390/pharmacy10040095

Immunol Cell Biol. 2022 Aug 25. doi: 10.1111/imcb.12581. Online ahead of print.

ABSTRACT

Alloreactive CD4+ T cells play a central role in allograft rejection. However, the post-transcriptional regulation of the effector program in alloreactive CD4+ T cells is unclear. N6 -methyladenosine (m6 A) RNA modification is involved in various physiological and pathological processes. Herein, we investigated whether m6 A methylation plays a role in the allogeneic T-cell effector program. m6 A levels of CD4+ T cells from spleens, draining lymph nodes and skin allografts were determined in a skin transplantation model. The effects of a METTL3 inhibitor STM2457 on CD4+ T-cell characteristics including proliferation, cell cycle, cell apoptosis and effector differentiation were determined after stimulation of polyclonal and alloantigen-specific (TEa; TCR transgenic) CD4+ T cells with α-CD3/α-CD28 mAbs and cognate CB6F1 alloantigen, respectively. We found that graft-infiltrating CD4+ T cells expressed high m6 A levels. Administration of STM2457 reduced m6 A levels, inhibited T-cell proliferation, and suppressed effector differentiation of polyclonal CD4+ T cells. Alloreactive TEa cells challenged with 40μM STM2457 exhibited deficits in T-cell proliferation and Th1 cell differentiation, a cell cycle arrest in the G0 phase, and elevated cell apoptosis. Moreover, these impaired T-cell responses were associated with the diminished expression levels of transcription factors Ki67, c-Myc and T-bet. Therefore, METTL3 inhibition reduces the expression of several key transcriptional factors for the T-cell effector program and suppresses alloreactive CD4+ T-cell effector function and differentiation. Targeting m6 A-related enzymes and molecular machinery in CD4+ T-cells represents an attractive therapeutic approach to prevent allograft rejection.

PMID:36005900 | DOI:10.1111/imcb.12581

Curr Issues Mol Biol. 2022 Aug 1;44(8):3455-3464. doi: 10.3390/cimb44080238.

ABSTRACT

The genetic factors of adult acute lymphoblastic leukemia (ALL) development are only partially understood. The Runt-Related Transcription Factor (RUNX) gene family play a crucial role in hematological malignancies, serving both a tumor suppressor and promoter function. The aim of this study was the assessment of relative RUNX1 and RUNX3 genes expression level among adult ALL cases and a geographically and ethnically matched control group. The relative RUNX1 and RUNX3 genes expression level was assessed by qPCR. The investigated group comprised 60 adult patients newly diagnosed with ALL. The obtained results were compared with a group of 40 healthy individuals, as well as clinical and hematological parameters of patients, and submitted for statistical analysis. ALL patients tend to have significantly higher RUNX1 gene expression level compared with controls. This observation is also true for risk group stratification where high-risk (HR) patients presented higher levels of RUNX1. A higher RUNX1 transcript level correlates with greater leukocytosis while RUNX3 expression is reduced in Philadelphia chromosome bearers. The conducted study sustains the hypothesis that both a reduction and increase in the transcript level of RUNX family genes may be involved in leukemia pathogenesis, although their interaction is complex. In this context, overexpression of the RUNX1 gene in adult ALL cases in particular seems interesting. Obtained results should be interpreted with caution. Further analysis in this research field is needed.

PMID:36005134 | DOI:10.3390/cimb44080238

Pharmacogenomics. 2022 Aug 25. doi: 10.2217/pgs-2022-0105. Online ahead of print.

NO ABSTRACT

PMID:36004680 | DOI:10.2217/pgs-2022-0105

Pharmacogenomics. 2022 Aug 25. doi: 10.2217/pgs-2022-0067. Online ahead of print.

ABSTRACT

Tweetable abstract It is well accepted that pharmacogenomics (PGx) information from Asia and Europe should not be applied to Africa. More work is needed on different ethnic groups to generate population-specific algorithms that can be used effectively and safely.

PMID:36004679 | DOI:10.2217/pgs-2022-0067

Cell Cycle. 2022 Aug 24:1-15. doi: 10.1080/15384101.2022.2109362. Online ahead of print.

ABSTRACT

High-grade serous ovarian cancer (HGSOC) is the most common and malignant type of ovarian cancer, accounting for 70%-80% of mortality. However, the treatment of HGSOC has improved little in the past few decades. Metformin is the first-line medication for the treatment of type 2 diabetes and has now gained more attention in cancer treatment. In this study, we sought to identify potential hub genes that metformin could target in the treatment of HGSOC. We downloaded GSE69428 and GSE69429 in the Gene Expression Omnibus database and performed the bioinformatics analysis. Subsequently, we analyzed the effect of Metformin in HGSOC through biological experiments. Molecular simulation docking was used to predict the interaction of Metformin and CCNE1. We chose CCNE1 for the study based on bioinformatics analysis, literature studies, and preliminary data. We evaluated that CCNE1 is overexpressed in HGSOC tissues and found that HGSOC cells with high CCNE1 expression increase sensitivity to Metformin treatment in the analysis of cell proliferation and anchorage-independent growth. Metformin could inhibit the expression of CCNE1, which is associated with the anti-proliferative effect of tumor cells. Moreover, Metformin could ameliorate the tumor growth in syngeneic orthotopic transplantation mouse models and xenograft tumorigenesis models. Furthermore, molecular simulation docking showed that Metformin may bind to CCNE1 protein, suggesting that CCNE1 could be a potential target for Metformin. Our data revealed that Metformin has antitumor effects on ovarian cancer and CCNE1 could be a potential target for Metformin.

PMID:36004387 | DOI:10.1080/15384101.2022.2109362

Front Pharmacol. 2022 Aug 8;13:891838. doi: 10.3389/fphar.2022.891838. eCollection 2022.

ABSTRACT

Human leukocyte antigen (HLA) proteins are present at the cellular surface of antigen-presenting cells and play a crucial role in the adaptive immune response. Class I genes, specifically certain HLA-B alleles, are associated with adverse drug reactions (ADRs) and are used as pharmacogenetic markers. Although ADRs are a common causes of hospitalization and mortality, the data on the prevalence of HLA-B pharmacogenetics markers in Arab countries are scarce. In this study, we investigated the frequencies of major HLA-B pharmacogenomics markers in the Qatari population. Next-generation sequencing data from 1,098 Qatari individuals were employed for HLA-B typing using HLA-HD version 1.4.0 and IPD-IMGT/HLA database. In addition, HLA-B pharmacogenetics markers were obtained from the HLA Adverse Drug Reaction Database. In total, 469 major HLA-B pharmacogenetic markers were identified, with HLA-B*51:01 being the most frequent pharmacogenetic marker (26.67%) in the Qatari population. Moreover, HLA-B*51:01 is associated with phenytoin- and clindamycin-induced ADRs. The second most frequent pharmacogenetic marker was the HLA-B*58:01 allele (6.56%), which is associated with allopurinol-induced ADRs. The third most frequent pharmacogenetic marker was the HLA-B*44:03 allele, which is associated with phenytoin-induced ADRs. The establishment of a pharmacogenetics screening program in Qatar for cost effective interventions aimed at preventing drug-induced hypersensitivity can be aided by the highly prevalent HLA-B pharmacogenetic markers detected here.

PMID:36003520 | PMC:PMC9393242 | DOI:10.3389/fphar.2022.891838

Clin Pharmacol Ther. 2022 Aug 24. doi: 10.1002/cpt.2730. Online ahead of print.

ABSTRACT

Thiopurine dose optimization by thiopurine-S-methyltransferase (TPMT) or nudix hydrolase-15 (NUDT15) significantly reduced the early leucopenia in Asia. However, it fails to avoid the late incidence (> 2 months). Although 6-thioguanine nucleotides (6TGN) was a makeshift in European, its function is controversial. In the present study, we aimed to explore whether DNA-thioguanine nucleotides (DNA-TG) in leukocytes, compared to 6TGN in erythrocytes, can be a better biomarker for late leucopenia. This was a prospective, observational study. Patients with inflammatory bowel disease (IBD) prescribed thiopurine from February 2019 to December 2019 were recruited. Thiopurine dose was optimized by NUDT15 C415T (rs116855232). DNA-TG and 6TGN levels were determined at the time of late leucopenia or 2 months after the stable dose obtained. A total of 308 patients were included. Thiopurine induced late leucopenia (WBC<3.5×109 /L) were observed in 43 patients (14.0%), who had significantly higher DNA-TG concentration than those without leucopenia (P=3.2×10-9, 423.3 (342.2~565.7) vs 270.5 (188.1~394.3) fmol/μg DNA). No difference of 6TGN concentrations between leucopenia and non-leucopenia was found. With a DNA-TG threshold of 340.1 fmol/μg DNA, 83.7% of leucopenia cases could be identified. Multivariate analysis showed DNA-TG was an independent risk factor for late leucopenia. Quantification of DNA-TG, rather than 6TGN, can be applied to gauge thiopurine therapy after NUDT15 screening in Chinese patients with IBD.

PMID:36002392 | DOI:10.1002/cpt.2730

Drug Metab Pers Ther. 2022 Aug 24. doi: 10.1515/dmpt-2022-0117. Online ahead of print.

ABSTRACT

OBJECTIVES: Timolol maleate is used for the treatment of glaucoma and metabolized by cytochrome CYP2D6 in the liver. The aim of this study was the evaluation of the influence of CYP2D6*4 and CYP2D6*10 gene polymorphisms on the safety of medications containing 0.5% of timolol maleate as glaucoma treatment in patients with primary open-angle glaucoma (POAG).

METHODS: 105 patients with POAG were prescribed glaucoma medications, containing 0.5% timolol maleate. The safety of glaucoma treatment was determined by electrocardiography (ECG) (to assess heart rate (HR) and PQ interval) and blood pressure (BP) measurements. The real-time polymerase chain reaction method was used for the detection of single nucleotide polymorphisms (SNP).

RESULTS: The risk of adverse drug reactions was higher in patients with the CYP2D6*4 GA genotype compared with GG: mean HR change at 1 month (2.88 ± 4.68 and 6.44 ± 5.57, p<0.001) and 6 months (5.14 ± 8.93 and 7.88 ± 5.65, p<0.001), mean PQ interval change at 1 (0.01 ± 0.031 and 0.02 ± 0.022, p=0.003) and 6 months (0.01 ± 0.032 and 0.02 ± 0.024, p=0.003). The risk of adverse drug reactions was higher in patients with the CYP2D6*10 CT genotype compared with CC: mean HR change at 1 month (2.94 ± 4.65 and 6.34 ± 5.66, p<0.001) and 6 months (5.20 ± 8.90 and 7.78 ± 5.75, p<0.001), mean PQ interval change at 1 (0.01 ± 0.032 and 0.02 ± 0.021, p=0.014) and 6 months (0.01 ± 0.033 and 0.02 ± 0.022, p=0.014).

CONCLUSIONS: CYP2D6*4 and CYP2D6*10 gene polymorphisms may affect a higher risk of timolol-induced bradycardia and increased PQ interval of treatment medications containing 0.5% of timolol maleate in patients with POAG.

PMID:36001461 | DOI:10.1515/dmpt-2022-0117

Curr Treat Options Oncol. 2022 Aug 24. doi: 10.1007/s11864-022-01010-x. Online ahead of print.

ABSTRACT

Pharmacogenomics is increasingly important to guide objective, safe, and effective individualised prescribing. Personalised prescribing has revolutionised treatments in the past decade, allowing clinicians to maximise drug efficacy and minimise adverse effects based on a person's genetic profile. Opioids, the gold standard for cancer pain relief, are among the commonest medications prescribed in palliative care practice. This narrative review examines the literature surrounding opioid pharmacogenomics and its applicability to the palliative care cancer population. There is currently limited intersection between the fields of palliative care and pharmacogenomics, but growing evidence presents a need to build linkages between the two disciplines. Pharmacogenomic evidence guiding opioid prescribing is currently available for codeine and tramadol, which relates to CYP2D6 gene variants. However, these medications are prescribed less commonly for pain in palliative care. Research is accelerating with other opioids, where oxycodone (CYP2D6) and methadone (CYP2B6, ABCB1) already have moderate evidence of an association in terms of drug metabolism and downstream analgesic response and side effects. OPRM1 and COMT are receiving increasing attention and have implications for all opioids, with changes in opioid dosage requirements observed but they have not yet been studied widely enough to be considered clinically actionable. Current evidence indicates that incorporation of pharmacogenomic testing into opioid prescribing practice should focus on the CYP2D6 gene and its actionable variants. Although opioid pharmacogenomic tests are not widely used in clinical practice, the progressively reducing costs and rapid turnover means greater accessibility and affordability to patients, and thus, clinicians will be increasingly asked to provide guidance in this area. The upsurge in pharmacogenomic research will likely discover more actionable gene variants to expand international guidelines to impact opioid prescribing. This rapidly expanding area requires consideration and monitoring by clinicians in order for key findings with clinical implications to be accessible, meaningfully interpretable and communicated.

PMID:36001223 | DOI:10.1007/s11864-022-01010-x

Pharmacogenomics. 2022 Aug 24. doi: 10.2217/pgs-2022-0064. Online ahead of print.

ABSTRACT

Pharmacogenetics is the relationship between an individual's genetic variations and their response to pharmacological treatment. We conducted an overview of reviews on the use of post-treatment pharmacogenetic testing for oncology, based on clinically relevant gene-drug pairs. We conducted a search on Medline, Embase and Cochrane Library, from their inception to 18 June 2020. We selected six eligible systematic reviews. The most studied drug categories were estrogen agonists/antagonists and fluoropyrimidines associated with cytochrome P450 and dihydropyrimidine dehydrogenase genes (CYP2D6 and DPYD), but many studies were classified as being of critically low or low quality. There is a need for more high-quality primary studies and systematic reviews that assess the risk of bias, with consistent definitions of clinical outcomes to consider the benefits of pharmacogenetic testing for oncology.

PMID:36001087 | DOI:10.2217/pgs-2022-0064