Pharmacogenomics最新文献

Background: Despite proven efficacy of statins in stroke prevention, genetic factors may influence individual stroke risk among statin users. With increasing precision medicine approaches and growing evidence of population-specific genetic variations, identifying genetic markers that predict stroke risk in statin-treated Asian populations has become critically important for personalized cardiovascular prevention strategies.

Methods: We conducted a genome-wide association study of 1,678 participants using lipid-lowering agents in the Korean Genome and Epidemiology Study (KoGES) cohort. Significant findings were replicated in 2,170 Asian participants on statins from the UK Biobank using an additive genetic model adjusted for relevant covariates.

Results: In the discovery analysis, 83 single nucleotide polymorphisms were suggestively associated with stroke (p <1.0 × 10^-5). Among these, 21 SNPs in the CDH13 gene were associated with increased stroke risk. The lead SNP, rs7201829, was significantly replicated in the UK Biobank (odds ratio: 2.29, p = 2.39 × 10^-5).

Conclusions: This study identified CDH13 as a significant genetic marker associated with stroke risk among Asian statin users. These findings provide the first genome-wide evidence for genetic determinants of stroke susceptibility during statin therapy, supporting the development of personalized prevention strategies in Asian populations.

Diabetes is a chronic disease that affects approximately 589 million people worldwide. Type 2 diabetes is one of its main forms (~90%) and manifests as hyperglycemia due to the resistance of myocytes and adipocytes to insulin. These are unable to capture and use blood glucose. In the long term, T2D can lead to a reduced production of insulin by beta cells, leading to more complex complications. Metformin is the first-line treatment for this condition. However, it may not always be effective for regulating blood glucose levels. Some factors, such as genetics, may influence the drug efficacy for this disease. The aim of this review is to summarize the pharmacogenetic variants associated with response to metformin in T2D treatment.

Your hospital has decided to introduce a pharmacogenomics program. What do you need to do to realize this ambition? In this paper, we set out the elements that should be considered, including the team and resources required to establish a sustainable program. This will draw on experience from successful global pharmacogenomic programs and will highlight key interdependencies, opportunities and challenges.

Background: Ensuring the efficacy and safety of medicines acting on the central nervous system (CNS) remains a challenge due to their complex pharmacokinetics and inter-individual variability in response. We describe the frequencies of pharmacogenomic variants affecting CNS drug metabolism in a Sri Lankan population.

Methods: Pharmacogenomic data pertaining to genes of interest were obtained from the Pharmacogenomics Knowledgebase database. Pharmacokinetically relevant cytochrome P450 isoforms were selected. Their frequencies in Sri Lankans were obtained from an anonymized database derived from 690 participants, from the Human Genetics Unit, Faculty of Medicine, University of Colombo. Minor allele frequencies (MAFs) of these variants were calculated and compared with other populations.

Results: MAFs of CYP2C19 rs4244285, CYP2D6 rs16947, CYP2D6 rs1058164, CYP2D6 rs1135840, and CYP2B6 rs3745274 were notably high at 40.9% (95%CI:38.3-43.5), 58.0% (95%CI:55.3-60.6), 43.8% (95%CI:41.1-46.4), 44.1% (95%CI:41.5-46.8), and 39.8% (95%CI:37.2-42.4), respectively. MAFs of CYP2C9 rs72558189, CYP2C19 rs4244285, CYP2D6 rs77913725, CYP2D6 rs1135828, and CYP2B6 rs3745274 recorded the highest in Sri Lankans when compared to all other populations. A lower prevalence was noted in MAFs of CYP2D6 rs1065852, CYP2D6 rs16947, and CYP2D6 rs28371706.

Conclusion: Sri Lankans exhibit an increased susceptibility to adverse reactions with common antidepressants, antipsychotics, and analgesics and reduced efficacy to opioid analgesics. These findings highlight the need for population-specific pharmacogenomic guidelines.

Background: Preemptive pharmacogenomic (PGx) testing is a candidate for broad implementation because of its potential to improve medication safety and outcomes. However, little is known about how patients may process preemptively generated PGx information.

Methods: We conducted a survey study in a cohort of 5,000 individuals receiving preemptive PGx testing in a primary care clinic in the USA. We assessed patients' perceived understanding of results and confidence in current prescription drugs and doses before and after they received PGx information.

Results: 4,624 individuals completed the pre-results survey (92.8% survey completion rate), and 3,408 (74.4% of pre-results survey completers) completed the post-results survey. Participants currently taking prescription medications were more likely to report inability to understand their PGx results. Additionally, participants' confidence in their current prescription drugs and drug doses declined following receipt of PGx results, and this decline was associated with number of prescriptions and perceived understanding of PGx results. Health literacy and educational attainment were not associated with reduced confidence.

Conclusion: As preemptive PGx testing is considered for implementation in primary care settings, care must be taken to support patients with preexisting prescriptions to ensure adequate understanding of the immediate relevancy and actionability of PGx results in their healthcare.

Background and aims: The SLCO gene family encodes OATP-like transporters that interact with statins and may influence their efficacy. Consequently, these genes are key targets in pharmacogenetic studies, and associations between SLCO1B1 variants and statin therapeutic response have already been demonstrated. The aim of this study was to evaluate the association between the SLCO1B1 gene polymorphisms rs2306283, rs11045819, rs4149056, and the SLCO1B3 gene polymorphism rs4149117, and the regularity of statin treatment.

Material and methods: This was a cohort study involving the review of 477 patient medical records and genotyping for the variants of interest. All patients were on simvastatin or atorvastatin therapy. Cox regression analysis was used to assess the association between genotypes and treatment regularity. Irregular treatment was defined by the occurrence of one or more of the following: 1) dose increase, 2) dose reduction, 3) treatment discontinuation, or 4) statin substitution.

Results: For rs2306283 (c.388A > G), carriers of the G allele had a significantly higher risk of treatment irregularities (Hazard Ratio: 1.50; 95% CI: 1.05-2.13; p = 0.024). For rs4149056 (c.521T > C), CC homozygotes showed a significantly increased risk of statin substitution and treatment discontinuation (Hazard Ratio: 2.16; 95% CI: 1.04-4.44; p = 0.037).

Conclusion: Our findings suggest an association between specific SLCO gene variants and irregularities in statin treatment.

Alzheimer's Disease (AD) represents a formidable challenge in neurology, characterized by progressive neurodegeneration and cognitive decline. Traditional therapeutic approaches have failed to deliver significant outcomes, underscoring the need for innovative paradigms such as precision medicine. The review explores integrating genomic, biomarker-driven, and individualized therapeutic strategies to tackle AD. It examines the role of key genetic factors, including APOE and MTHFR polymorphisms, in influencing disease susceptibility and treatment responses. Advances in biomarker technologies, such as blood-based and imaging biomarkers, are highlighted for their potential in early diagnosis and patient stratification. Additionally, the review underscores the importance of tailoring interventions across different stages of AD, incorporating lifestyle modifications and emerging tools like artificial intelligence & recent patented technologies. Precision medicine offers a transformative pathway, aiming to deliver personalized, effective care that addresses the complex and multifactorial nature of AD. The paradigm shift promises improved clinical outcomes and enhanced patient quality of life.

Introduction: Fentanyl overdose is a public health crisis in the United States, as fentanyl was implicated in nearly 70% of drug overdose deaths in 2023. To provide insight into genetic factors that may influence risk of fentanyl overdose, we conducted a scoping review of associations between cytochrome P450 3A4 (CYP3A4) and 3A5 (CYP3A5) genetic variants and relevant phenotypes.

Areas covered: We searched databases through August 2025 for peer-reviewed studies of human subjects or postmortem samples, and integrated evidence from 64 genetic association studies that analyzed single nucleotide polymorphisms in CYP3A4 or CYP3A5. We considered a diverse range of phenotypes relevant to fentanyl overdose, including opioid overdose, fentanyl pharmacokinetics and pharmacodynamics, opioid use (disorder), and pharmacotherapy response.

Expert opinion and commentary: Evidence from 64 studies suggested that the no-function CYP3A5 * 3 (rs776746) allele contributes to increased fentanyl overdose risk, with strongest support coming from studies of fentanyl pharmacokinetics in clinical settings. There was less robust evidence for the role of CYP3A4 variants (e.g. rs2242480). Future research should prioritize prospective genotyping of at-risk populations, development of models that integrate pharmacogenetics with psychiatric genetics, and large-scale harmonization of relevant datasets.

Aim: To examine whether patients with depression or chronic/acute pain understand the results of pharmacogenomic testing they had done as part of clinical research.

Methods: Semi-structured interviews were conducted with 45 patients who underwent pharmacogenomic testing and subsequently received their testing results by mail. These interviews assessed whether participants were aware that they had testing, how this testing impacted their current medications, and whether they grasped the future significance of this testing. A grounded theory approach was used to analyze this interview data.

Results: All of our participants were aware that they had underwent medical testing and 23 (51%) were aware that this testing was genetic and was used to guide medication management. Almost all of our participants believed it was important to share their results with future providers and 24 (53%) recognized that their results could impact future medication management. Thirteen (29%) participants stated that their results found medicines they should avoid and eight named specific medicines they believed should be avoided based on their results.

Conclusion: Although our participants exhibited a general understanding of their pharmacogenomic results, we found that they lacked a sufficient understanding of how these results specifically impacted their current and future healthcare.

Breast cancer is the most common malignancy in women worldwide. While personalized treatment options are obstructed by the limitations of conventional biopsy follow-up, the liquid biopsy could detect the tumor's characteristics in order to reach a more targeted therapy for metastatic breast cancer patients. The aim of this article is to review the characteristics of the liquid biopsy in the follow-up of metastatic breast cancer patients. A comprehensive literature search was conducted using the PubMed literature to retrieve topic-related articles using keywords 'metastatic breast cancer,' 'liquid biopsy' and 'follow up.' A descriptive analysis was undertaken, and 29 original articles were retained. The study of blood biomarkers is being used in the monitoring and follow-up of metastatic breast cancer. It is used to determine the survival rate based on different biomarkers and monitor the response to treatment through the status of the tumor. This review describes the latest findings on breast cancer's circulating tumor cells, circulating cell-free DNA, circulating tumor DNA, proteomes, and extracellular vesicles (exosomes) in the plasma. Our literature review revealed that the liquid biopsy is capable of detecting breast cancer biomarkers in order to monitor breast cancer patients, improve their treatment choices and predict their prognosis more accurately.