Ann Hum Genet. 2025 May 13:e12601. doi: 10.1111/ahg.12601. Online ahead of print.

ABSTRACT

Pharmacogenomics, the use of germline genomic data to guide prescription to improve effective and safer medication, holds promise as a clinical intervention. To date in most health systems, there has been limited uptake of pharmacogenomic testing confined to a few single drug-gene associations. Here, we describe the current reactive model of single gene testing and the potential for this to change to a pre-emptive panel or genome-based approach. For this change to occur, three major challenges need to be addressed-the pharmacogenomic testing approach, the digital and data integration, and service delivery models. We explore some of the potential solutions and how pharmacogenomics can be integrated into routine care at scale for patient benefit.

PMID:40358420 | DOI:10.1111/ahg.12601

Cells. 2025 Apr 22;14(9):622. doi: 10.3390/cells14090622.

ABSTRACT

In the original publication [...].

PMID:40358202 | DOI:10.3390/cells14090622

Front Pharmacol. 2025 Apr 28;16:1539870. doi: 10.3389/fphar.2025.1539870. eCollection 2025.

ABSTRACT

BACKGROUND: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have emerged as promising therapeutics for heart failure (HF). Nevertheless, evidence supporting the mechanism of SGLT2i efficacy in HF patients is currently limited. Genetic variation in SLC5A2 (encoding SGLT2) may influence HF progression and SGLT2i response, as well as inform potential SGLT2i mechanisms. Thus, this study investigated associations between SLC5A2 variation and clinical outcomes in SGLT2i-naïve and dapagliflozin-treated HF cohorts.

METHODS: We analyzed two HF cohorts to identify variants associated with SGLT2i response pathways. Adjusted Cox proportional-hazard regression models were used to assess the effect of SLC5A2 variation on a primary composite outcome of cardiovascular (CV) hospitalization or all-cause mortality in SGLT2i-naïve patients, and HF hospitalization or CV death in dapagliflozin-treated patients. The initial cohort comprised 327 American HF patients naïve to SGLT2i throughout the study. Subsequently, a prospective cohort study of 190 Egyptian SGLT2i-naïve HF patients treated with dapagliflozin was analyzed. In this cohort, SNPs in UGT2B4 and SLC2A1 were also investigated. Changes in NT-proBNP levels, KCCQ-12 scores, echocardiographic parameters, and eGFR throughout 6-month follow-up were tested with linear regression models as secondary outcomes.

RESULTS: In SGLT2i-naïve patients, rs3813008 (SLC5A2) was significantly associated with reduced risk of the composite outcome of all-cause death or hospitalization (HR = 0.65, 95% CI: 0.47-0.89, P = 0.008). In the dapagliflozin-treated cohort, rs3813008 was also associated with death or hospitalization, but with increased risk in treated patients (HR = 3.38, 95% CI: 1.35-8.42, P = 0.008).

CONCLUSION: Our study suggests that SLC5A2 variation is associated with clinical outcomes in SGLT2i-naïve and treated HF patients, warranting further investigation of SLC5A2 and SGLT2i interactions.

PMID:40356983 | PMC:PMC12066643 | DOI:10.3389/fphar.2025.1539870

Future Oncol. 2025 May 13:1-14. doi: 10.1080/14796694.2025.2501517. Online ahead of print.

ABSTRACT

AIMS: This study identifies single-nucleotide polymorphisms (SNPs) associated with cellular response to cyclophosphamide (CTX) using phosphoramide mustard (PM), its primary cytotoxic metabolite, and explores the downstream consequences for breast cancer (BC) patients.

METHODS: We analyzed 1,978,545 SNPs from EBV-transformed lymphoblastic cell lines (LCLs) derived from 53 unrelated European individuals, in a genome-wide association study using cellular PM sensitivity data. We filtered SNPs associated with PM sensitivity (p < 5 × 10-5) predicted to overlap with regulatory elements in breast tissue using a chromatin state prediction model. We then assessed the consequences using LCL transcriptomic data and data from BC patients treated with (ACT-BC; N = 155) and without CTX.

RESULTS: Twenty SNPs were filtered out including rs12408401, which was associated with PM resistance (p = 3.89 × 10-5), potentially disrupted a CTCF-loop, and was associated with increased RFX5 expression (p = 0.036), which was associated with poor disease-free interval in ACT-BC patients (HR = 5.32; p = 0.028); and rs784562, which was associated with improved PM sensitivity (p = 6.41 × 10-6), potentially altered nearby enhancer functionality, and reduced expression of KRT72 which was associated with poor progression-free survival in ACT-BC patients (HR = 3.61; p = 0.040).

CONCLUSION: Our study identifies SNPs significantly associated with cellular CTX response with potential mechanistic and clinical relevance, thereby providing insights toward optimized CTX treatment strategies.

PMID:40356407 | DOI:10.1080/14796694.2025.2501517

J Psychopharmacol. 2025 May 12:2698811251337387. doi: 10.1177/02698811251337387. Online ahead of print.

ABSTRACT

INTRODUCTION: Psychopharmacotherapy with mirtazapine is commonplace. Lower serum concentrations of mirtazapine were reported in smokers due to CYP1A2 induction. However, no previous study that investigated CYP1A2 genetics and mirtazapine treatment considered CYP1A2-inducing parameters.

AIM: We aimed to investigate the association of CYP1A2 variants, mirtazapine serum concentration, and treatment outcome, considering the smoking status of the patients.

METHODS: Two depression cohorts were investigated for the association between serum concentration and treatment response of mirtazapine and CYP1A2-163C>A (rs762551) and -3860G>A (rs2069514) genotype groups, also considering smoking status, sex, and age of the patients. In total, 124 patients (82 non-smokers and 42 smokers) were eligible for the analyses.

RESULTS: Dose-corrected serum concentration (CD) of mirtazapine was associated with smoking status, sex, and age, with lower CD in smokers, females, and older patients. Considering non-smokers and genotype-grouped smokers, CD of mirtazapine in CYP1A2 normal metabolizer smokers (N = 6) did not differ from CD of non-smokers. By contrast, smokers carrying the CYP1A2*1A/*1F and *1F/*1F genotype groups showed 34.4% and 33.4% lower mirtazapine CD compared to non-smokers.

DISCUSSION: As yet, for clinical practice, it may be more relevant to focus on smoking status than on the CYP1A2 gene variants. Considering the relevant impact of smoking on the mirtazapine CD, physicians should monitor an increase in side effects due to the expected increase in mirtazapine serum concentrations. In these cases, measurement of mirtazapine CD and/or subsequent dosage reduction is recommended. The clinical relevance of CYP1A2 genotyping prior to treatment with drugs metabolized by CYP1A2 needs further investigation.

PMID:40353511 | DOI:10.1177/02698811251337387

Curr Protein Pept Sci. 2025 May 8. doi: 10.2174/0113892037364237250402151440. Online ahead of print.

ABSTRACT

The COVID-19 outbreak, caused by the SARS-CoV-2 coronavirus, has threatened and taken many lives since the end of 2019. Given the importance of COVID-19 worldwide, since its spread, many research groups have been seeking blood markers that could help to understand the disease establishment and prognosis. Usually, those markers are proteins with a differential accumulation only during infection. Based on that, proteomic studies have played a crucial role in elucidating diseases. Mass spectrometry (MS) is a promising technique in COVID-19 studies, allowing the identification and quantification of proteins present in the plasma or serum of affected patients. It helps us to understand pathological mechanisms, predict clinical outcomes, and develop specific therapies. MS proteomics revealed biomarkers associated with infection, disease severity, and immune response. Plasma or blood serum is easy to collect and store; however, its composition and the higher concentration of proteins (e.g., albumins) shadow the identification of less abundant proteins, which usually are essential markers. So, clean-up approaches such as depletion strategies and fractionating are often required to analyze blood samples, allowing the identification of low-abundant proteins. This review will discuss many proteomic approaches to discovering new plasma biomarkers of COVID-19 employed in recently published studies. The challenges inherent to blood samples will also be discussed, such as sample preparation, data processing, and identifying reliable biomarkers.

PMID:40353410 | DOI:10.2174/0113892037364237250402151440

Alzheimers Dement (Amst). 2025 May 9;17(2):e70111. doi: 10.1002/dad2.70111. eCollection 2025 Apr-Jun.

ABSTRACT

INTRODUCTION: The apolipoprotein E (APOE) ɛ4 allele is a well-established risk factor for neurocognitive impairment (NCI), with varying impacts between men and women. This study investigates the distinct roles of sex and gender in modifying APOE ɛ4-related NCI.

METHODS: Biological sex was inferred from sex chromosomes, and a femininity score (FS) was used as a proxy for gender. We analyzed 276,596 UK Biobank participants without prior NCI to assess whether sex and FS modified the effect of APOE ɛ4 on NCI.

RESULTS: NCI risk was higher in APOE ɛ4 carriers compared to non-carriers (hazard ratio [HR] = 2.48 in females; HR = 1.96 in males) with significant interaction by sex (P < 0.0001). FS was associated with an increased NCI risk after accounting for sex (HR = 1.07, 95% confidence interval: 1.04-1.10, P < 0.0001) with no significant differences by sex or APOE ɛ4 carrier status.

DISCUSSION: Our findings show that APOE ɛ4 increases NCI risk more in females, while FS independently elevates risk across sexes.

HIGHLIGHTS: Apolipoprotein E (APOE) ɛ4 increases neurocognitive impairment (NCI) risk, with a greater impact in females (hazard ratio [HR] = 2.48) than males (HR = 1.96).Sex significantly modifies the effect of APOE ɛ4 on NCI (P < 0.0001f).Femininity score increases NCI risk (HR = 1.07) independently of sex and APOE ɛ4.Understanding the distinct sex and gender contributions to APOE ɛ4-related NCI can improve interventions.

PMID:40352685 | PMC:PMC12064333 | DOI:10.1002/dad2.70111

Clin Pharmacol Ther. 2025 May 11. doi: 10.1002/cpt.3691. Online ahead of print.

ABSTRACT

The cytochrome P450 2D6 (CYP2D6) metabolizes around 20% of currently prescribed medications, including the antipsychotic risperidone. Previous studies reported greater odds of switching antipsychotic medication from risperidone among CYP2D6 poor metabolizers (PM) without considering treatment duration up to the switch. Risperidone treatment failure, defined as risperidone treatment duration up to switching medication, was analyzed among 515 patients of the PsyMetab cohort using Kaplan-Meier estimates with log-rank tests and Cox multivariate regression. Risperidone-to-paliperidone ratios were higher among CYP2D6 PMs (median: 2.78) vs. the other phenotypes (median: 0.14, P < 0.001). After 1 year of treatment, the proportion of patients who switched from risperidone was 44%. This proportion was increased to 70% among PMs, vs. 42% among the other CYP2D6 phenotypes (P = 0.026). PMs' risk of switching increased over time (interaction PM*treatment duration: 1.01; P = 0.011), becoming statistically significant after 3 months of treatment, with 1.79 (P = 0.028), 3.7 times (P < 0.001) and 16.3 times higher (P = 0.001) risk of switch at 3, 6, and 12 months, respectively (95% confidence intervals: 1.07-3.01, 1.91-7.17, and 3.13-85.37, respectively). Considering a pharmacogenetic-guided treatment, the number of patients needed to genotype to find one PM and lower the switching proportion from 70% to 42% would be 65. In conclusion, CYP2D6 PM status presented an increased risk of switching from risperidone over 1 year of treatment, the risk increasing over time and becoming statistically significant after the first 3 months of treatment.

PMID:40350722 | DOI:10.1002/cpt.3691

Adv Med Sci. 2025 May 9:S1896-1126(25)00025-2. doi: 10.1016/j.advms.2025.05.001. Online ahead of print.

ABSTRACT

PURPOSE: Ferritin amounts that accumulate in the meconium may provide new postnatal insights into intrauterine iron homeostasis and neonatal preparedness for the postnatal period. The most dynamic increases in fetal iron stores and fetal growth occur during the third trimester.

MATERIALS AND METHODS: This study involved 122 neonates born between 36 and 41 weeks of gestation, with birth weights from 2,650 g to 4,960 g and birth lengths ranging from 50 cm to 60 cm. Ferritin amounts per gram of meconium were determined via ELISA in the first meconium passed after birth.

RESULTS: A significant week-by-week increase in the birth weight and length (p<0.05) was accompanied by decreasing meconium ferritin amounts (p=0.021) across the gestational age range of 36-41 weeks. There were negative correlations (p<0.05) between the systematic decrease in meconium ferritin amounts and the gestational age across the same range (r = -0.18) and between ferritin amounts and the birth weight and length of newborns (r= -0.20 and r= -0.31). Neonates born at 36-37 weeks of gestation had lower birth weight and length, while their meconium ferritin amounts were nearly twice as high as in neonates born at 38-39 weeks or 40-41 weeks (p<0.05).

CONCLUSIONS: Systematic decreases in meconium ferritin amounts from 36 to 41 weeks of gestation may suggest a gradual and gestational age-appropriate maturation of the mechanisms responsible for adaptation of the fetus to postnatal life. Determining a cut-off value for meconium ferritin amounts could aid in optimal management of newborns after birth.

PMID:40349924 | DOI:10.1016/j.advms.2025.05.001

Ann Clin Microbiol Antimicrob. 2025 May 10;24(1):32. doi: 10.1186/s12941-025-00799-3.

ABSTRACT

BACKGROUND: This study examines colistin resistance in Gram-negative bacteria in Egypt, analyzing prevalence, trends, geographic variations, colistin-carbapenem resistance correlation, and mcr-mediated plasmid resistance.

METHODS: We conducted a systematic search of articles published between 2014 and 2024 that reported on colistin or mcr-mediated resistance in Gram-negative bacteria isolated from human infections in Egypt, with clearly defined susceptibility testing methods. A random-effects meta-analysis was conducted to estimate colistin resistance prevalence based on broth microdilution (BMD) findings, the gold standard method. To explore the influence of study-level factors-including alternative susceptibility testing methods-a multivariate meta-regression analysis was performed. The results of the meta-regression are reported as regression coefficients (β), representing the difference in colistin resistance, expressed in percentage points. All statistical analyses were conducted using R software.

RESULTS: This analysis included 55 studies. Based on BMD susceptibility testing, colistin resistance was observed in 9% of all recovered Gram-negative isolates (95% CI: 6-14%) and was significantly higher among carbapenem-resistant isolates (31%, 95% CI: 25-38%), with p < 0.001. Multivariate meta-regression analysis further confirmed that colistin resistance was significantly higher in carbapenem-resistant isolates compared to the total recovered isolates (β = 9.8% points, p = 0.001). Additionally, colistin resistance has significantly increased over time, with a β = 1.8% points per year (p = 0.001). The use of the VITEK 2 system was associated with lower detected colistin resistance compared to BMD (β = -7.0, p = 0.02). Geographically, resistance rates were higher in Upper Egypt (β = 9.3, p = 0.04). Regarding mcr plasmid-mediated resistance, mcr-1 was the most prevalent resistance gene, particularly in E. coli. In contrast, mcr-2 was rare, detected sporadically in K. pneumoniae and P. aeruginosa.

CONCLUSION: In Egypt, BMD testing identified colistin resistance in 9% of Gram-negative bacteria, increasing to 31% in carbapenem-resistant isolates. This higher resistance in carbapenem-resistant strains suggests stronger selective pressure from frequent colistin use. Additionally, colistin resistance has shown a rising trend over time, likely driven by increased usage and the spread of plasmid-mediated resistance. These findings underscore the urgent need for strict antimicrobial stewardship and alternative therapies to curb resistance evolution.

PMID:40349047 | DOI:10.1186/s12941-025-00799-3

Psychiatr Clin North Am. 2025 Jun;48(2):257-264. doi: 10.1016/j.psc.2025.01.004. Epub 2025 Mar 4.

ABSTRACT

Pharmacogenomic (PGx) testing is an evidence-based strategy to optimize the selection and dosing of certain psychotropic medications. An individual's genetics play a role in medication response through pharmacokinetic and pharmacodynamic mechanisms. The current evidence base of psychiatric PGx mainly focuses on the metabolism of psychotropics through the cytochrome P450 (CYP) system. PGx testing and decision support tools are not yet standardized, resulting in variations in interpretation and prescribing recommendations. Clinicians are encouraged to use PGx results as part of the clinical picture, in addition to the patient's overall clinical profile, in determining a personalized treatment plan for their patients.

PMID:40348416 | DOI:10.1016/j.psc.2025.01.004

EBioMedicine. 2025 May 9;116:105745. doi: 10.1016/j.ebiom.2025.105745. Online ahead of print.

ABSTRACT

BACKGROUND: People with schizophrenia differ in the type and severity of symptoms experienced, as well as their response to medication. A better understanding of the factors that influence this heterogeneity is necessary for the development of individualised patient care. Here, we sought to investigate the relationships between phenotypic severity and both medication and pharmacogenomic variables in a cross-sectional sample of people with schizophrenia or schizoaffective disorder depressed type.

METHODS: Confirmatory factor analysis derived five dimensions relating to current symptom severity (positive symptoms, negative symptoms of diminished expressivity, negative symptoms of reduced motivation and pleasure, depression and suicide) and cognitive ability in participants prescribed with antipsychotic medication. Linear models were fit to test for associations between medication and pharmacogenomic variables with dimension scores in the full sample (N = 585), and in a sub-sample of participants prescribed clozapine (N = 215).

FINDINGS: Lower cognitive ability was associated with higher chlorpromazine-equivalent daily antipsychotic dose (β = -0.12; 95% CI, -0.19 to -0.05; p = 0.001) and with the prescription of clozapine (β = -0.498; 95% CI, -0.65 to -0.35; p = 3 × 10-10) and anticholinergic medication (β = -0.345; 95% CI, -0.55 to -0.14; p = 8 × 10-4). We also found associations between pharmacogenomics-inferred cytochrome P450 (CYP) enzyme activity and symptom dimensions. Increased genotype-predicted CYP2C19 and CYP3A5 activity were associated with reduced severity of the positive (β = -0.108; 95% CI, -0.19 to -0.03; p = 0.009) and both negative symptom dimensions (β = -0.113; 95% CI, -0.19 to -0.03; p = 0.007; β = -0.106; 95% CI, -0.19 to -0.02; p = 0.012), respectively. Faster predicted CYP1A2 activity was associated with higher cognitive dimension scores in people taking clozapine (β = 0.17; 95% CI, 0.05-0.29; p = 0.005).

INTERPRETATION: Our results confirm the importance of taking account of medication history (and particularly antipsychotic type and dose) in assessing potential correlates of cognitive impairment or poor functioning in patients with schizophrenia. We also highlight the potential for pharmacogenomic variation to be a useful tool to help guide drug prescription, although these findings require further validation.

FUNDING: Medical Research Council (MR/Y004094/1) and The National Center for Mental Health, funded by the Welsh Government through Health and Care Research Wales. SKL was funded by a PhD studentship from Mental Health Research UK (MHRUK). DBK, JTRW, MCOD and AFP were supported by the European Union's Horizon 2020 research and innovation programme under grant agreement 964874.

PMID:40347835 | DOI:10.1016/j.ebiom.2025.105745

Clin Transl Sci. 2025 May;18(5):e70246. doi: 10.1111/cts.70246.

ABSTRACT

Pharmacogenomics remains underutilized in pediatric oncology, despite the existence of evidence-based guidelines. Implementation of pharmacogenomics-informed prescribing could improve medication safety and efficacy in pediatric oncology patients, who are at high risk of adverse drug reactions. This study examines the prevalence of high-risk pharmacogenomic phenotypes and the prescription of relevant medications in a diverse Australian pediatric oncology cohort, highlighting the potential impact of pharmacogenomic testing in this unique population. Whole genome sequencing data from 180 patients were analyzed to assess 14 genes with evidence-based pharmacogenomic guidelines relevant to pediatric oncology. Over 90% of patients had at least one high-risk phenotype, with 20% presenting four or more. Ondansetron, mercaptopurine, omeprazole, pantoprazole, and voriconazole were commonly prescribed medications that have pharmacogenomic prescribing recommendations, with the latter three showing the highest actionability rates. High-risk phenotypes were most frequently observed for CYP2C19 and CYP2D6, with 30% of patients having a high-risk phenotype for both genes. This study underscores the potential utility of pharmacogenomics in pediatric oncology patients across a range of pharmacogenes and commonly prescribed medications. The findings support advocacy for implementing broad, pre-emptive pharmacogenomic testing in oncology patients to improve treatment safety and efficacy.

PMID:40347484 | DOI:10.1111/cts.70246

Mol Pain. 2025 May 10:17448069251343417. doi: 10.1177/17448069251343417. Online ahead of print.

ABSTRACT

Calcium channels play an essential role in the molecular and physiological mechanisms underlying anesthesia by mediating intracellular calcium ion (Ca²⁺) flux, which regulates key processes such as neurotransmitter release, neuronal excitability, and immune responses. Voltage-gated calcium channels (VGCCs) and ligand-gated calcium channels (LGCCs) are integral to the anesthetic process, with subtypes such as T-type VGCCs and NMDA receptors influencing consciousness and pain perception. This review emphasizes current evidence to highlight how anesthetic agents interact with calcium channels via direct inhibition and modulation of intracellular signaling pathways, such as phosphatidylinositol metabolism.Additionally, calcium channelopathies-genetic or acquired dysfunctions affecting VGCCs and LGCCs-pose challenges in anesthetic management, including arrhythmias, malignant hyperthermia, and altered anesthetic sensitivity. These findings underscore the critical need for precision medicine approaches tailored to patients with these conditions. While significant progress has been made in understanding the roles of calcium channels in anesthesia, knowledge gaps remain regarding the long-term implications of anesthetic interactions on calcium signaling and clinical outcomes.This review bridges foundational science with clinical practice, emphasizing the translational potential of calcium channel research for optimizing anesthetic strategies. By integrating molecular insights with emerging pharmacogenomic approaches, it provides a pathway for developing safer and more effective anesthesia protocols that enhance patient outcomes.

PMID:40346957 | DOI:10.1177/17448069251343417

Fundam Clin Pharmacol. 2025 Jun;39(3):e70013. doi: 10.1111/fcp.70013.

ABSTRACT

BACKGROUND: Opioid use disorder (OUD) is an emerging and global public health concern, and its management remains inadequate, notably due to a lack of biomarkers, except for the CYP2B6 genetic polymorphisms.

OBJECTIVES: Hence, the aim of this study was to assess the influence of genetic polymorphisms of ABCB1, SLC22A1, COMT, and OPRM1 on biological parameters and clinical response in patients receiving methadone maintenance treatment (MMT).

METHODS: A subgroup of 72 patients treated by MMT was genotyped for ABCB1 (rs1045642; rs2032582), SLC22A1 (rs12208357; rs72552763; rs113569197), COMT (rs4680), and OPRM1 (rs1799971) from Opioid PhArmacoLogy (OPAL), a clinical survey of patients suffering from OUD. Associations of these polymorphisms and both clinical and pharmacological (plasma methadone levels) responses were investigated.

RESULTS: All polymorphisms tested were not associated with (R,S)-methadone concentrations/doses (concentrations relative to doses), (R)-methadone concentrations/doses nor (S)-methadone concentrations/doses in bivariate analyses with codominant and recessive models. Also, polymorphisms tested were not related to clinical response (opiate cessation) during MMT in treated patients. The main limitations of our study were the sample size and the absence of polygenic analyses.

CONCLUSION: This study found no evidence to support the use of genotyping for polymorphisms in the ABCB1, SLC22A1, COMT, and OPRM1 genes in a clinical setting for the management of MMT in OUD.

PMID:40346879 | DOI:10.1111/fcp.70013

BMC Genomics. 2025 May 9;26(1):462. doi: 10.1186/s12864-025-11676-w.

ABSTRACT

Glucocorticoids, acting through the glucocorticoid receptor (GR), control metabolism, maintain homeostasis, and enable adaptive responses to environmental challenges. Their function has been comprehensively studied, leading to identification of numerous tissue-specific GR-dependent mechanisms. Abundant evidence shows that GR-triggered responses differ across tissues, however, the extent of this specificity was not comprehensively explored. It is also unknown how particular GR-induced molecular patterns are translated into profile of higher-level human traits. Here, we examine cross-tissue effects of GR activation on gene expression. We assessed changes induced by stimulation with GR agonist, dexamethasone in nine tissues (adrenal cortex, perigonadal adipose tissue, hypothalamus, liver, kidney, anterior thigh muscle, pituitary gland, spleen, and lungs) in adult male C57BL/6 mice, using whole-genome microarrays. Dexamethasone induced balanced transcriptional responses across all examined tissues with 585 identified dexamethasone-regulated transcripts, including 446 with significant treatment-tissue interaction effects. Clustering analysis revealed sixteen GR-dependent patterns, including those universal across tissues and tissue-specific. We leveraged existing gene annotations and created new annotation sets based on chromatin immunoprecipitation sequencing, recent large-scale genome-wide association studies, and human transcriptome collections. As expected, GR-dependent transcripts were associated with essential metabolic processes (glycolysis/gluconeogenesis, lipid-metabolism) and inflammation-related pathways. Beyond these, we found novel links between regulated gene patterns and human phenotypic traits, like reticulocyte count or blood triglyceride levels. Overall effects of GR stimulation are well coordinated and closely linked to biological roles of tissues and organs. Our findings provide novel insights into complex systemic and tissue-specific actions of glucocorticoids and their potential impacts on human physiology and pathology.

PMID:40346507 | DOI:10.1186/s12864-025-11676-w

Nurs Clin North Am. 2025 Jun;60(2):321-332. doi: 10.1016/j.cnur.2024.12.009. Epub 2025 Feb 6.

ABSTRACT

Antibiotics have revolutionized medicine, but their use is not without challenges. The efficacy and safety of antibiotics can vary significantly among individuals due to genetic differences. Genetic variation can influence the risk of antibiotic-related adverse effects, and understanding genetics can improve our ability to identify and manage these risks. Pharmacogenomics, the study of how genes affect a person's response to drugs, is emerging as a crucial field in optimizing antibiotic therapy. Pharmacogenomic elements may have a potential role in optimizing drug therapy and reducing adverse drug reactions.

PMID:40345763 | DOI:10.1016/j.cnur.2024.12.009

Nurs Clin North Am. 2025 Jun;60(2):305-320. doi: 10.1016/j.cnur.2024.12.007. Epub 2025 Feb 20.

ABSTRACT

Pharmacogenomics (PGx)-the study of how one's genes affect their response to drugs-has implications for every medical subspecialty, including cardiology. This article discusses evidence-based resources that provide guidance for interpreting and applying PGx results in patient care. All health care providers, including frontline nurses, should understand this important tool for patient care.

PMID:40345762 | DOI:10.1016/j.cnur.2024.12.007

Nurs Clin North Am. 2025 Jun;60(2):293-304. doi: 10.1016/j.cnur.2024.12.006. Epub 2025 Jan 18.

ABSTRACT

Pharmacogenomics (PGx) offers a personalized approach to treating mental health disorders, like depression, by using an individual's genetic profile to guide medication selection and dosage. This approach can reduce trial-and-error prescribing, shorten time to remission, and decrease adverse side effects. Nurses, as frontline healthcare providers, play a crucial role in educating patients about PGx testing and incorporating it into care. There are many clinical resources available to assist with decision making when integrating PGx into routine care. As PGx testing advances, nurses must stay updated on emerging practices to optimize treatment strategies, improving patient outcomes and quality of life in mental health care.

PMID:40345761 | DOI:10.1016/j.cnur.2024.12.006

Nurs Clin North Am. 2025 Jun;60(2):283-292. doi: 10.1016/j.cnur.2025.01.006. Epub 2025 Feb 15.

ABSTRACT

In the new and evolving area of precision medicine, the nurse will not only have to rely on the 5 rights for medication administration but may also have to take into account the patient's genetic makeup. The 5 rights of medication administration have been incorporated into precision medicine, which includes pharmacogenetics-the specific gene and drug interaction- or more broadly, pharmacogenomics, which encompasses specific gene and drug interactions and other genetic and environmental factors. Pharmacogenomic testing is now available with specific guidelines to assist the prescriber with drug and dose selection to improve drug efficacy and reduce adverse drug reactions.

PMID:40345760 | DOI:10.1016/j.cnur.2025.01.006