Pharmacogenomics最新文献

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.

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.

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.

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.

Rationale: Preemptive pharmacogenetic (PGx) testing offers a promising approach to personalized antidepressant treatment by identifying genetic variations influencing drug metabolism. By focusing on CYP2D6 and CYP2C19 genes, this strategy aims to improve treatment response, minimize adverse effects, and optimize dosing in patients with depression.

Objectives and methods: This systematic review evaluates the effectiveness of preemptive PGx testing, primarily for CYP2D6 and CYP2C19, in enhancing antidepressant treatment outcomes. A comprehensive search of databases, including PubMed and Embase, was conducted to identify relevant studies. The review included randomized controlled trials and meta-analyses that assessed PGx testing in relation to treatment response and remission. Data on clinical outcomes were extracted and analyzed.

Results: PGx testing led to improved antidepressant response rates and remission at 8- and 12-week follow-ups compared to treatment-as-usual (TAU). However, where data were available, benefits were less pronounced after six months of follow-up. The findings suggest that PGx testing plays an important role in achieving earlier remission, while TAU requires a longer time to achieve remission.

Conclusion: Preemptive pharmacogenetic testing for CYP2D6 and CYP2C19 could enhance early antidepressant treatment outcomes, offering a valuable tool for personalized medicine. Further research is required to explore implementation challenges in diverse clinical settings.

Inflammatory bowel disease (IBD) poses a major therapeutic challenge due to its chronic course and variable treatment responses. Genetic polymorphisms significantly influence drug efficacy, prompting this review to analyze their role in treatment non-response. A systematic literature search (PubMed/Scopus) using terms like "genetic polymorphism," "non-response," and "IBD" identified 25 relevant studies. Key findings linked TNFα (-308 G > A), TNFRSF1A, and TNFRSF1B polymorphisms to reduced anti-TNFα therapy effectiveness. TPMT variants correlated with thiopurine toxicity, while CYP3A4 and CYP3A5 polymorphisms altered tacrolimus metabolism. These genetic markers could serve as predictive tools for personalized IBD treatment, emphasizing the potential of genetic screening in clinical practice. Future research should integrate multi-omics approaches to refine predictive models and advance precision medicine, ultimately improving patient outcomes through tailored therapeutic strategies.

Introduction: Rosuvastatin has become a good choice in the statin group because it has shown greater efficacy in reducing lipid levels than other statins, allowing patients to reach their therapeutic goal more quickly. To date, research has shown a broad relationship between the kinetics and efficacy of this drug and the phenotype of two transporters, OATP1B1 and BCRP, encoded by SLCO1B1 and ABCG2 genes. However, there are many other genes whose variation may also affect the treatment.

Objective: To conduct a systematic review including all information on the kinetics, measured by AUC and C_max parameters; efficacy, by reduction in lipid levels and carotid intima-media thickness; and safety of rosuvastatin, by the occurrence of adverse events.

Methods: A search of the published literature was conducted in PubMed using the term "rosuvastatin AND pharmacogenetics" (PROSPERO code: CRD420251041953).

Results: A total of 37 articles were included, investigating 40 genes.

Conclusions: The importance of ABCG2 in drug kinetics and efficacy and of SLCO1B1 in kinetics is confirmed, as is the possible association of CYP3A5 with efficacy and safety and of APOC1 with efficacy. There are also positive results for other genes that should be studied further to confirm their association with rosuvastatin.

Colorectal cancer is one of the most prevalent cancers worldwide. We have thus focused on studies on the association of genetic polymorphisms with treatment response and adverse effects in colorectal cancer patients. This review highlights the inter-individual and inter-population genetic variations in ABC transporters and their association with variability in drug response. Several studies report the association of specific ABC transporter gene polymorphisms with the risk of developing colorectal carcinoma and the clinical outcomes in patients undergoing chemotherapy. It is important to understand genetic polymorphisms and genetic profiling for colorectal cancer patients in the context of personalized medication. This review is built on a comprehensive knowledge of the pharmacogenetics of colorectal carcinoma with a special focus on ABC polymorphism.

Aims: Dihydropyrimidine dehydrogenase (DPYD) plays a critical role in the metabolism of fluoropyrimidine-based chemotherapies such as 5-fluorouracil (5-FU), capecitabine, and tegafur. Genetic variants in DPYD can lead to partial or complete enzyme deficiency, resulting in toxic accumulation of these drugs and severe, sometimes fatal, adverse reactions.

Materials & methods: Whole‑exome sequencing data from 1,612 individuals were analyzed for DPYD variants. Variants were classified as decreased, no function, or potentially deleterious. Comparative allele frequency analysis was performed using global population datasets to identify inter-population differences.

Results and conclusion: A total of 95 individuals (5.3%) carried at least one decreased or no function DPYD variant, indicating a significant prevalence of clinically actionable genotypes in this Indian cohort. The most frequent variant, c.1236 G > A (HapB3), was found in 53 individuals (3.28%), supporting its relevance in the Indian population. Comparative analysis revealed distinct population patterns and novel variants not captured in current guidelines. These results support the urgency in implementing preemptive DPYD genotyping to avoid adverse drug reactions and further studies to gather evidence on rare and novel variants in the Indian population. To the best of our knowledge, this is the largest population analysis of DPYD variants from India.