Pharmacogenomics. 2025 Jan 14:1-4. doi: 10.1080/14622416.2025.2452835. Online ahead of print.

ABSTRACT

AIMS: Clopidogrel exhibits substantial variability in therapeutic response, largely contributed by genetic factors. The pharmacogenomic variants data on clopidogrel metabolism in South Asians have been sparsely studied. This study explores the impact of CYP2C19 and CES1 gene variants on clopidogrel metabolism in Sri Lankans, revealing significant pharmacogenomic insights with broader implications for South Asians.

MATERIALS & METHODS: Genotype data were filtered out from an anonymized database of 690 Sri Lankans, and minor allele frequencies (MAFs) were calculated. Five variants of CYP2C19 and one variant of CES1 gene were studied.

RESULTS: Among the five CYP2C19 variants studied, rs12769205 (A>G) and rs4244285 (G>A) had the highest MAF of 42.1% and 42.0%, respectively. The CES1 variant rs71647871 (C>T) showed a MAF of 0.2%. Sri Lankans exhibited significantly higher MAFs for key variants compared to populations such as Europeans, African Americans, and East Asians (p < 0.05).

CONCLUSION: Given that South Asians share genetic similarities, these findings suggest that a substantial proportion of the region's population may also be poor responders to clopidogrel, increasing the risk of adverse outcomes. This highlights the importance of genotype-guided antiplatelet therapy, which could improve clinical outcomes across South Asia amidst rising cardiovascular disease rates.

PMID:39809701 | DOI:10.1080/14622416.2025.2452835

Anesth Pain Med (Seoul). 2025 Jan 15. doi: 10.17085/apm.24067. Online ahead of print.

ABSTRACT

Immunonutrition, which uses specific nutrients to modulate the immune response, has emerged as a vital adjunct to perioperative care. Surgery-induced stress triggers immune responses that can lead to complications, such as infections and delayed wound healing. Traditional nutritional support often overlooks the immunological needs of surgical patients. Immunonutrition addresses this oversight by providing key nutrients, such as arginine, omega-3 fatty acids, glutamine, nucleotides, and antioxidants (vitamins C and E) to enhance immune function and support tissue repair. This review examined the efficacy and safety of immunonutrition in surgical settings, guided by the recommendations of the American Society for Parenteral and Enteral Nutrition and the European Society for Clinical Nutrition and Metabolism. Both organizations recommend immunonutrition for high-risk or malnourished patients undergoing major surgery and support its use in reducing complications and improving recovery. The key nutrients in immunonutrition aim to improve immune cell function, reduce inflammation, and enhance wound healing. Clinical studies and meta-analyses have demonstrated that immunonutrition lowers the infection rate, shortens the length of hospital stay, and accelerates recovery. Challenges hindering the clinical application of immunonutrition include cost, logistics, and a lack of standardized and personalized protocols. Future studies should focus on biomarker-driven approaches, pharmacogenomics, and innovative nutrient formulations. Addressing these issues will help to integrate immunonutrition into clinical practice, ultimately improving surgical outcomes and patient recovery.

PMID:39809503 | DOI:10.17085/apm.24067

Clin Transl Sci. 2025 Jan;18(1):e70125. doi: 10.1111/cts.70125.

ABSTRACT

Monoclonal antibodies (mAbs) are critical components in the therapeutic landscape, but their dosing strategies often evolve post-approval as new data emerge. This review evaluates post-marketing label changes in dosing information for FDA-approved mAbs from January 2015 to September 2024, with a focus on both initial and extended indications. We systematically analyzed dosing modifications, categorizing them into six predefined groups: Dose increases or decreases, inclusion of new patient populations by body weight or age, shifts from body weight-based dosing to fixed regimens, and adjustments in infusion rates. Among the 86 mAbs evaluated, 21% (n = 18) exhibited changes in dosing information for the initial indication, with a median time to modification of 37.5 months (range: 5-76 months). Furthermore, for mAbs with extended indications (n = 26), 19.2% (n = 5) underwent dosing changes in their first extensions, with a median time to adjustment of 31 months (range: 8-71 months). Key drivers for these adjustments included optimizing therapeutic efficacy, addressing safety concerns, accommodating special populations, and enhancing patient convenience. We also discuss the role of model-informed drug development, real-world evidence, and pharmacogenomics in refining mAb dosing strategies. These insights underscore the importance of ongoing monitoring and data integration in the post-marketing phase, providing a foundation for future precision medicine approaches in mAb therapy.

PMID:39807701 | DOI:10.1111/cts.70125

BMJ Open. 2024 Dec 20;14(12):e092164. doi: 10.1136/bmjopen-2024-092164.

ABSTRACT

INTRODUCTION: Compared with the guideline-recommended use of low-molecular weight heparin (LMWH) for 28 days to prevent venous thromboembolism (VTE) after cytoreductive surgery, oral rivaroxaban avoids the pain and inconvenience of daily injections and reduces medical expenses. The proposed randomised controlled trial (RCT) aims to compare the efficacy and safety of rivaroxaban and enoxaparin in preventing VTE in patients after surgery for gynaecological malignancies and to provide a reference for clinical medication prevention.

METHODS AND ANALYSIS: This is a single-centre, randomised, controlled, open-label and assessor-blind clinical trial. Patients undergoing surgery for gynaecological malignancies will be randomly assigned in a 1:1 ratio to an oral rivaroxaban study group and a subcutaneous injection enoxaparin control group for anticoagulant prophylaxis. The medication administration begins 12-24 hours after surgery and continues for 28 days, with a 30-day follow-up after surgery. Clinical events during the treatment and the follow-up period will be observed. The primary endpoint will be any VTE. Secondary endpoints will be any bleeding event, medication compliance rate, rivaroxaban pharmacokinetics and pharmacogenomics. The sample size required for the G-alfalfa trial is derived based on power calculations of the VTE incidence in the two intervention regimens in previous literature.

ETHICS AND DISSEMINATION: This study was approved by the Ethics Committee of Fujian Maternal and Child Health Hospital on 2 April 2024 (Approval No.:2023KY174-03). The results of the trial will be submitted for publication in a peer-reviewed journal and presented at relevant conferences.

TRIAL REGISTRATION NUMBER: Chinese Clinical Trial Registry (ChiCTR) 2300078535.

PMID:39806649 | DOI:10.1136/bmjopen-2024-092164

BMC Med Educ. 2025 Jan 14;25(1):63. doi: 10.1186/s12909-025-06651-8.

ABSTRACT

BACKGROUND: Individuals often respond differently to medications, giving rise to the field of precision medicine (PM), which focuses on tailoring treatments to individual genetic, environmental, and lifestyle factors. This study examined the level of comfort healthcare professional students have with their knowledge of precision medicine, alongside their attitudes and perceptions toward precision medicine, at a tertiary institution in Nigeria.

METHODS: A cross-sectional questionnaire-based study was conducted among healthcare professional students (400-600 level) at the University of Nigeria Nsukka between January and March 2024. The data were analyzed via IBM Statistical Product and Service Solutions (SPSS) for Windows version 27. Descriptive analyses (frequency, percentage, mean, and standard deviation) and chi-square tests were used to summarize and compare the variables. Statistical significance was set at p < 0.05.

RESULTS: A total of 431 healthcare professional students participated in this study. Fewer than half (n = 200, 46.4%) were pharmacy students, and the majority were within the age range of 21-25 years (n = 288, 66.8%). Nearly half (n = 206, 47.8%) reported having information about precision medicine from the internet, and the majority (n = 341, 79.1%) expressed having an interest in a career involving research in precision medicine. More than half of the students (n = 240, 55.7%) were comfortable with their knowledge of precision medicine and had favourable attitudes (n = 236, 54.8%). Additionally, more than half had positive perceptions of ethical concerns (n = 216, 50.1%) and education in precision medicine (n = 239, 55.5%). Gender, age, department, level of study, awareness of PM, and interest in a career involving research were significantly associated with students' knowledge, attitudes, and perceptions of precision medicine (p < 0.001).

CONCLUSION: Healthcare professional students were comfortable with their knowledge of PM and, in addition, had favourable attitudes and positive perceptions toward the use of precision medicine.

PMID:39806360 | DOI:10.1186/s12909-025-06651-8

Sci Rep. 2025 Jan 13;15(1):1824. doi: 10.1038/s41598-024-84744-y.

ABSTRACT

This study was designed to assess the effect of brentuximab vedotin on several breast cancer cell lines in terms of promoting apoptosis and managing cancer progression. Additionally, the study investigated the potential of repurposing this drug for new therapeutic reasons, beyond its original indications. The study evaluates the cytotoxic effects of Brentuximab vedotin across five cell lines: normal human skin fibroblasts (HSF), three breast cancer cell lines (MCF-7, MDA-MB-231, and T-47D), and histiocytic lymphoma (U-937). Brentuximab treatment was administered at four time points (0, 24, 48, and 72 h), with cell viability assessed at each interval. HSF cells, serving as controls, exhibited minimal viability loss (above 70%), indicating limited toxicity in normal fibroblasts. In contrast, MCF-7 and MDA-MB-231 cells demonstrated time-dependent reductions in viability, with a pronounced decline by 72 h, suggesting Brentuximab's efficacy in both ER-positive and triple-negative breast cancer. T-47D cells also showed decreased viability, though at a slower rate. U-937 cells exhibited the most substantial reduction, highlighting Brentuximab's potent activity against hematologic malignancies. Wound healing assays further revealed that Brentuximab significantly impaired the migration and healing capacity of cancer cells compared to untreated controls. Additionally, cell cycle analysis indicated G2/M phase arrest in cancer cells, particularly in MCF-7 and MDA-MB-231, while HSF cells remained largely unaffected. Apoptosis detection confirmed Brentuximab-induced cell death, with significant increases in late apoptosis in cancer lines, especially by 72 h. Gene expression analysis revealed upregulation of pro-apoptotic genes (BAX, Caspase 3, and Caspase 9) in cancer cells, alongside a decrease in anti-apoptotic BCL-2 expression. These findings suggest Brentuximab's selective cytotoxicity against cancer cells and its potential as an effective therapeutic agent, particularly in breast cancer and histiocytic lymphoma.

PMID:39805861 | DOI:10.1038/s41598-024-84744-y

BMJ Support Palliat Care. 2025 Jan 13:spcare-2024-005205. doi: 10.1136/spcare-2024-005205. Online ahead of print.

ABSTRACT

CONTEXT: Pharmacogenomics (PGx) is an area of expanding research, which could indicate whether an individual is likely to benefit from a symptom control medication. Palliative and supportive care (PSC) could be an area that benefits from PGx, however, little is known about the current evidence base for this.

OBJECTIVE: To determine how PGx can be applied in PSC, whether there is any evidence of benefit, and to understand the extent and type of evidence that supports the use of PGx in PSC.

METHODS: A search of six databases up to July 2024. Reference snowballing from review articles and screened papers was used to identify any missed articles.

RESULTS: 11 articles were reviewed. A total of 550 patients had a PGx test across 8/11 studies. Up to half of the patients had an actionable PGx result, and in one study there were 4.6 drug-gene interactions per patient. Implementation of PGx was found to be feasible. Clinician adherence to advice given was under-reported. No studies reported health economics analysis, or was designed to definitively answer whether PGx was better than standard care.

CONCLUSIONS: It is both feasible and acceptable to conduct PGx testing in a supportive and palliative care setting. Many supportive care medications are amenable to PGx. Clinician adherence to recommendations is variable and there is no clear evidence that PGx enhances palliative/supportive care patient outcomes. Prospective, clinical trials are needed to establish whether PGx can improve symptom management for people receiving PSC.

PMID:39805678 | DOI:10.1136/spcare-2024-005205

Discov Oncol. 2025 Jan 13;16(1):39. doi: 10.1007/s12672-024-01616-7.

ABSTRACT

The occurrence and progression of breast cancer (BCa) are complex processes involving multiple factors and multiple steps. The tumor microenvironment (TME) plays an important role in this process, but the functions of immune components and stromal components in the TME require further elucidation. In this study, we obtained the RNA-seq data of 1086 patients from The Cancer Genome Atlas (TCGA) database. We calculated the proportions of tumor-infiltrating immune cells (TICs) and immune and stromal components using the CIBERSORT and ESTIMATE methods, and we screened differentially expressed genes (DEGs). Univariate Cox regression analysis of overall survival was performed on the DEGs, and a protein-protein interaction network of their protein products was generated. Finally, the hub gene CD5 was obtained. High CD5 expression was found to be associated with longer survival than low expression. Gene set enrichment analysis showed that DEGs upregulated in the high-CD5 expression group were mainly enriched in tumor- and immune-related pathways, while those upregulated in the low-expression group were enriched in protein export and lipid synthesis. TIC analysis showed that CD5 expression was positively correlated with the infiltration of CD8+ T cells, activated memory CD4+ T cells, gamma delta T cells, and M1 macrophages and negatively correlated with the infiltration of M2 macrophages. CD5 can increase anticancer immune cell infiltration and reduce M2 macrophage infiltration. These results suggest that CD5 is likely a potential prognostic biomarker and therapeutic target, providing novel insights into the treatment and prognostic assessment of BCa.

PMID:39804513 | DOI:10.1007/s12672-024-01616-7

Endocr Connect. 2025 Jan 1:EC-24-0617. doi: 10.1530/EC-24-0617. Online ahead of print.

ABSTRACT

BACKGROUND: Arterial hypertension and left ventricular hypertrophy and remodeling are independent cardiovascular risk factors in patients with Cushing's syndrome. Changes in the renin-angiotensin system and in the mineralocorticoid axis activity could be involved as potential mechanisms in their pathogenesis, in addition to cortisol excess.

METHODS: In this ancillary study of our previous study prospectively investigating patients with ACTH-dependent Cushing's syndrome by cardiac magnetic resonance imaging (NCT02202902), 11 patients without any interfering medication were cross-sectionally compared to 20 control subjects matched for age, sex and body mass index. Angiotensin metabolites and adrenal steroids were measured by liquid chromatography tandem mass spectrometry and their relation to blood pressure and cardiac structure was evaluated.

RESULTS: Concentrations of angiotensin I and angiotensin II were comparable, but the angiotensin-converting enzyme activity was significantly lower (2.19 (1.67;3.08) vs 4.07 (3.1;5.6); p<0.001) in patients compared to controls. Aldosterone concentrations were significantly lower (6.9 (6.9;124.1) vs 239.9 (181.4;321.9) pmol/l; p<0.001) in the group of patients, but adrenal aldosterone precursor metabolites were comparable between patients and controls. Inverse correlations were observed for 24h urinary free cortisol and aldosterone with the ratio of left ventricular mass to end-diastolic volume (r=0.470, p=0.012 and r= -0.367, p=0.046, respectively).

CONCLUSIONS: We describe a disease specific profile of angiotensin metabolites in patients with ACTH dependent Cushing's syndrome. Low levels of aldosterone in the presence of unchanged precursor metabolites indicate a direct inhibitory action of cortisol excess on the aldosterone synthase. Further, glucocorticoid excess per se drives cardiac muscle remodeling.

PMID:39804209 | DOI:10.1530/EC-24-0617

Allergy Asthma Clin Immunol. 2025 Jan 12;21(1):3. doi: 10.1186/s13223-024-00945-0.

ABSTRACT

BACKGROUND: Nasal allergen provocation tests are an important part of the diagnostics of allergic diseases triggered by environmental factors. Recently, increased attention has been paid to the potential use of this method in the diagnosis of food allergy. The objective of the study was to evaluate the usefulness of the nasal allergen provocation test in a group of subjects allergic to hen's egg white allergens.

METHODS: The material consisted of a group of 57 subjects (32 subjects with hen's egg white allergy and 25 healthy controls). The method consisted in a nasal allergen provocation test carried out with the use of hen's egg white allergen and assessed using the visual analog scale and optical rhinometry as well as by determination of sIgE and tryptase levels in nasal lavage fluid.

RESULTS: Subjective nasal symptoms and objective evaluations following the application of 100 µg of hen's egg white allergen revealed a moderately positive nasal mucosal response in optical rhinometry tests (ΔE = 0.34 OD).

CONCLUSIONS: Nasal food challenge with hen's egg white allergen is a good diagnostic alternative in the group of food allergy patients. Due to the insufficient number of studies carried out so far, further attempts at standardization of the method are required.

PMID:39800752 | DOI:10.1186/s13223-024-00945-0

J Affect Disord. 2025 Jan 10:S0165-0327(25)00044-8. doi: 10.1016/j.jad.2025.01.032. Online ahead of print.

ABSTRACT

PURPOSE: The risk of suicide among individuals with bipolar disorder (BD) is among the highest of all psychiatric disorders. The etiology of suicidality is complex and multifactorial, with genetic factors playing a prominent role according to twin-, family-, and molecular genetic studies. This study examines polygenic risk scores from adult studies in relation to suicidality in youth with or at risk for BD.

METHODS: Primary analyses examined the association of polygenic risk scores for suicide attempt, based on adult genome-wide association study data, with suicidal ideation, self-harm, and suicide attempt in 232 youth (mean age 16.7 years), including 125 with, and 107 at high-risk for, BD. We also tested polygenic risk scores for risk tolerance, schizophrenia, major depressive disorder, BD, and attention-deficit hyperactivity disorder in secondary analyses.

RESULTS: Polygenic risk scores for suicide attempt were not significantly associated with suicidal ideation, self-harm, or suicide attempt. Higher polygenic risk scores for major depressive disorder were nominally associated with increased risk of suicidal ideation in the overall sample (beta = 0.36, se(beta) = 0.16, p = 0.017), controlling for covariates.

IMPLICATIONS: Our finding that polygenic risk for depression is associated with suicidal ideation converges with prior findings in youth and adults. While present findings are constrained by sample size, they underscore the importance of undertaking genome-wide association studies in youth, rather than relying solely on prior adult genome-wide association studies.

PMID:39800071 | DOI:10.1016/j.jad.2025.01.032

Pharmacol Res. 2025 Jan 9:107575. doi: 10.1016/j.phrs.2024.107575. Online ahead of print.

ABSTRACT

Statins are first-line treatments in the primary and secondary prevention of cardiovascular disease. Clinical studies show statins act independently of lipid-lowering mechanisms to decrease C-reactive protein (CRP), an inflammation marker. We aim to elucidate genetic loci associated with CRP statin response. CRP statin response is the change in log-CRP between off-treatment and on-treatment measurements. Cohort-level Genome-Wide Association Studies (GWAS) of CRP response were performed using 1000 Genomes imputed data, testing ~10 million common genetic variants. GWAS meta-analysis combined results from seven cohorts and clinical trials totalling 14,070 statin-treated individuals of European ancestry within the GIST consortium. Secondary analyses included statin-by-placebo interaction analyses, and lookups in African ancestry cohorts. Our GWAS identified two genome-wide significant (P<5e-8) loci: APOE and HNF1A for CRP statin response corrected for baseline CRP. The missense lead variant rs429358 at APOE, contributing to the APOE-E4 haplotype, is a risk locus for dyslipidaemia, Alzheimer's and coronary artery disease (CAD). The HNF1A locus is associated with diabetes, cholesterol levels, and CAD. Both loci are also associated with baseline CRP levels, and neither locus achieved a significant (P<0.05) result from the statin v. placebo interaction meta-analysis using randomized clinical trial data. However, the interaction result (P-int=0.09) for APOE was suggestive and possibly underpowered. The APOE-E4 signal may therefore be associated with both CRP and LDL-cholesterol statin response. Combined with suggestions in the literature that APOE also leads to differential statin benefit in Alzheimer's, the APOE locus warrants further investigation for potential genetic effects on healthcare with statin treatment.

PMID:39798939 | DOI:10.1016/j.phrs.2024.107575

J Clin Med. 2024 Dec 25;14(1):24. doi: 10.3390/jcm14010024.

ABSTRACT

Background/Objectives: Periodontitis is an inflammatory disease induced by bacteria in dental plaque that can activate the host's immune-inflammatory response and invade the bloodstream. We hypothesized that a higher periodontal inflamed surface area (PISA) is associated with higher levels of inflammatory biomarkers, lower levels of antioxidants, and mitochondrial DNA copy number (mtDNAcn). Methods: Using periodontal parameters, we calculated the PISA score, measured the levels of inflammatory biomarkers and antioxidants in the serum, and took buccal swabs for mtDNA and nuclear DNA (nDNA) extraction. Results: Higher PISA was associated with higher CRP levels, higher leukocyte, neutrophil, and erythrocyte counts, and lower magnesium-to-calcium ratio, but not with mtDNAcn. A higher number of deep pockets was associated with higher leukocytes and neutrophil counts and higher uric acid levels. Conclusions: The PISA score might be an appropriate parameter to assess the inflammatory burden of periodontitis, but not to assess mitochondrial dysfunction after mtDNA isolation from buccal swabs.

PMID:39797107 | DOI:10.3390/jcm14010024

Int J Mol Sci. 2024 Dec 30;26(1):260. doi: 10.3390/ijms26010260.

ABSTRACT

Statins are the primary drugs used to prevent cardiovascular disease by inhibiting the HMG-CoA reductase, an enzyme crucial for the synthesis of LDL cholesterol in the liver. A significant number of patients experience adverse drug reactions (ADRs), particularly musculoskeletal problems, which can affect adherence to treatment. Recent clinical guidelines, such as those from the Clinical Pharmacogenetics Implementation Consortium (CPIC) in 2022, recommend adjusting rosuvastatin doses based on genetic variations in the ABCG2 and SLCO1B1 genes to minimize ADRs and improve treatment efficacy. Despite these adjustments, some patients still experience ADRs. So, we performed a candidate gene study to better understand the pharmacogenetics of rosuvastatin. This study included 119 healthy volunteers who participated in three bioequivalence trials of rosuvastatin alone or in combination with ezetimibe at the Clinical Trials Unit of the Hospital Universitario de La Princesa (UECHUP). Participants were genotyped using a custom OpenArray from ThermoFisher that assessed 124 variants in 38 genes associated with drug metabolism and transport. No significant differences were observed according to sex or biogeographic origin. A significant increase in t1/2 (pmultivariate(pmv) = 0.013) was observed in the rosuvastatin plus ezetimibe trial compared with the rosuvastatin alone trials. Genetic analysis showed that decreased (DF) and poor function (PF) volunteers for the ABCG2 transporter had higher AUC∞/DW (adjusted dose/weight), AUC72h/DW and Cmax/DW compared to normal function (NF) volunteers (pmv< 0.001). DF and PF volunteers for SLCO1B1 showed an increase in AUC72h/DW (pmv = 0.020) compared to increased (IF) and NF individuals. Results for ABCG2 and SLCO1B1 were consistent with the existing literature. In addition, AUC∞/DW, AUC72h/DW and Cmax/DW were increased in intermediate (IA) and poor (PA) NAT2 acetylators (pmv = 0.001, pmv< 0.001, pmv< 0.001, respectively) compared to rapid acetylators (RA), which could be associated through a secondary pathway that was previously unknown.

PMID:39796117 | DOI:10.3390/ijms26010260

Int J Mol Sci. 2024 Dec 26;26(1):103. doi: 10.3390/ijms26010103.

ABSTRACT

Asthma is a common complex disease with susceptibility defined through an interplay of genetic and environmental factors. Responsiveness to asthma treatment varies between individuals and is largely determined by genetic variability. The polygenic score (PGS) approach enables an individual risk of asthma and respective response to drug therapy. PGS models could help to predict the individual risk of asthma using 26 SNPs of drug pathway genes involved in the metabolism of glucocorticosteroids (GCS), and beta-2-agonists, antihistamines, and antileukotriene drugs associated with the response to asthma treatment within GWAS were built. For PGS, summary statistics from the Trans-National Asthma Genetic Consortium GWAS meta-analysis, and genotype data for 882 individuals with asthma/controls from the Volga-Ural region, were used. The study group was comprised of Russian, Tatar, Bashkir, and mixed ethnicity individuals with asthma (N = 378) aged 2-18 years. and individuals without features of atopic disease (N = 504) aged 4-67 years from the Volga-Ural region. The DNA samples for the study were collected from 2000 to 2021. The drug pathway genes' PGS revealed a higher odds for childhood asthma risk (p = 2.41 × 10-12). The receiver operating characteristic (ROC) analysis showed an Area Under the Curve, AUC = 0.63. The AUC of average significance for moderate-to-severe and severe asthma was observed (p = 5.7 × 10-9, AUC = 0.64). Asthma drug response pathway gene variant PGS models may contribute to the development of modern approaches to optimise asthma diagnostics and treatment.

PMID:39795959 | DOI:10.3390/ijms26010103

BMC Psychiatry. 2025 Jan 10;25(1):34. doi: 10.1186/s12888-025-06481-4.

ABSTRACT

BACKGROUND: Few new psychiatric drugs have entered the market in recent decades; in contrast, the number of drugs carrying pharmacogenomic labels continues to increase. For the foreseeable future, the advancement of psychiatry and drug therapy may hinge on personalized treatment. Currently, antipsychotic or antidepressant choices rely heavily on the clinical experience of psychiatrists and potentially lengthy iterative trials. During these trials, the clinical response to treatment in acutely depressed patients can be assessed only after several weeks of exposure to the drug. Although pharmacogenomic testing has been used in clinical care for several years, most Chinese clinicians struggle to utilize the information accurately, resulting in expensive tests that provide little real benefit to patients. Here, we demonstrate how to combine the results of pharmacogenomic testing to develop an individualized treatment plan. Our goal is to find the optimal medication regimen and dosage for the patient in the shortest possible time, control symptoms as soon as possible, and predict adverse drug reactions. This approach aims to offer a practical therapeutic idea for clinical practice.

CASE PRESENTATION: We present the case of a 27-year-old female patient experiencing a relapse of depression. Despite previous attempts with empiric medication, her symptoms remained uncontrolled, leading to exacerbation and drug withdrawal reactions. Utilizing the results of pharmacogenetic testing, we crafted an individualized treatment plan, resulting in rapid remission without any adverse drug reactions.

CONCLUSION: Recognizing the complexity of antidepressant response, our patients aim to improve their understanding, as well as that of other healthcare providers, by undergoing pharmacogenomics testing. This enhances the credibility of their medication choices. While pharmacogenomics is just one aspect considered in selecting a treatment regimen for depression, it remains a valuable tool for increasing credibility and mitigating potential adverse events.

PMID:39794795 | DOI:10.1186/s12888-025-06481-4

Pediatr Neonatol. 2024 Dec 29:S1875-9572(24)00231-6. doi: 10.1016/j.pedneo.2024.06.015. Online ahead of print.

ABSTRACT

BACKGROUND: Invasive mechanical ventilation in very-low-birth-weight infants (VLBWI) was associated with immediate and long-term complications. Nasal high-frequency oscillation (nHFO) has recently become a new non-invasive ventilation (NIV) mode for treating respiratory failure in VLBWI. This study aimed to investigate the safety and efficacy of nHFO as an alternative respiratory support to prevent intubation in VLBWI.

METHODS: A retrospective analysis was conducted using the clinical data of 42 VLBWIs with respiratory distress syndrome (RDS) who were treated in our department from August 2018 to August 2020 and met the selection criteria.

RESULTS: nHFO was used as a rescue strategy in 32 infants and a prophylactic strategy in 10 infants. It was observed that out of 42 cases, 30 cases (71.4%) were able to avoid intubation within 72 h, while 23 cases (54.8%) were successfully switched to another NIV mode from nHFO. There was a significant decrease in pCO2 and an increase in pH 1 h after using nHFO in the success group. Two cases (4.8%) of feeding intolerance associated with nHFO were noted.

CONCLUSION: This study showed that nHFO as alternative respiratory support for preterm infants with RDS might be safe and effective in reducing the need for intubation.

PMID:39794186 | DOI:10.1016/j.pedneo.2024.06.015

Nicotine Tob Res. 2025 Jan 10:ntaf009. doi: 10.1093/ntr/ntaf009. Online ahead of print.

ABSTRACT

INTRODUCTION: Varenicline is an α4β2 nicotinic acetylcholine receptor partial agonist with the highest therapeutic efficacy of any pharmacological smoking cessation aid and a 12-month cessation rate of 26%. Genetic variation may be associated with varenicline response, but to date no genome-wide association studies of varenicline response have been published.

METHODS: In this study, we investigated the genetic contribution to varenicline effectiveness using two electronic health record-derived phenotypes. We defined short-term varenicline effectiveness (SVE) and long-term varenicline effectiveness (LVE) by assessing smoking status at 3 and 12 months, respectively, after initiating varenicline treatment. In Stage 1, comprising five European cohort studies, we tested genome-wide associations with SVE (1,405 cases, 2,074 controls) and LVE (1,576 cases, 2,555 controls), defining sentinel variants (the most strongly associated variant within 1 megabase) with p-value <5×10-6 to follow up in Stage 2. In Stage 2, we tested association between sentinel variants and comparable smoking cessation endpoints in varenicline randomised controlled trials. We subsequently meta-analysed Stages 1 and 2.

RESULTS: No variants reached genome-wide significance in the meta-analysis. In Stage 1, 10 sentinel variants were associated with SVE and five with LVE at a suggestive significance threshold (p-value <5×10-6); none of these sentinels were previously implicated in varenicline-aided smoking cessation or in genetic studies of smoking behaviour.

CONCLUSIONS: We provide initial insights into the biological underpinnings of varenicline-aided smoking cessation, through implicating genes involved in various processes, including gene expression, cilium assembly and early-stage development.

IMPLICATIONS: Leveraging electronic health records, we undertook the largest genetic study of varenicline-aided smoking cessation to date, and the only such study to test genome-wide associations. We showed distinct genetic variants associated (p-value <5×10-6) with varenicline-aided smoking cessation which implicate diverse cellular functions, including transcriptional regulation, RNA modification and cilium assembly. These provide insights which, if independently corroborated, will improve understanding of varenicline response. The growing availability of biobank resources with genetic and varenicline response data will provide future opportunities for larger studies using the approach we developed.

PMID:39792440 | DOI:10.1093/ntr/ntaf009

J Appl Genet. 2025 Jan 10. doi: 10.1007/s13353-024-00930-8. Online ahead of print.

ABSTRACT

Gilles de la Tourette syndrome (GTS) and other tic disorders (TDs) have a substantial genetic component with their heritability estimated at between 60 and 80%. Here we propose an oligogenic risk score of TDs using whole-genome sequencing (WGS) data from a group of Polish GTS patients, their families, and control samples (n = 278). In this study, we first reviewed the literature to obtain a preliminary list of 84 GTS/TD candidate genes. From this list, 10 final risk score genes were selected based on single-gene burden tests (SKAT p < 0.05) between unrelated GTS cases (n = 37) and synthetic control samples based on a database of local allele frequencies. These 10 genes were CHADL, DRD2, MAOA, PCDH10, HTR2A, SLITRK5, SORCS3, KCNQ5, CDH9, and CHD8. Variants in and in the vicinity (± 20 kbp) of the ten risk genes (n = 7654) with a median minor allele frequency in the non-Finnish European population of 0.02 were integrated into an additive classifier. This risk score was then applied to healthy and GTS-affected individuals from 23 families and 100 unrelated healthy samples from the Polish population (AUC-ROC = 0.62, p = 0.02). Application of the algorithm to a group of patients with other tic disorders revealed a continuous increase of the oligogenic score with healthy individuals with the lowest mean, then patients with other tic disorders, then GTS patients, and finally with severe GTS cases with the highest oligogenic score. We have further compared our WGS results with the summary statistics of the Psychiatric Genomics Consortium genome-wide association study (PGC GWAS) of TDs and found no signal overlap except for the CHADL gene locus. Polygenic risk scores from common variants of GTS GWAS show no difference between patient and control groups, except for the comparison between patients with non-GTS TDs and patients with severe GTS. Overall, we leveraged WGS data to construct a GTS/TD risk score based on variants that may cooperatively contribute to the aetiology of these disorders. This study provides evidence that typical and severe adult GTS as well as other tic disorders may exist on a single spectrum in terms of their genetic background.

PMID:39792217 | DOI:10.1007/s13353-024-00930-8

Expert Opin Drug Metab Toxicol. 2025 Jan 10. doi: 10.1080/17425255.2025.2451440. Online ahead of print.

ABSTRACT

INTRODUCTION: The prevalence of polypharmacy and the increasing availability of pharmacogenetic information in clinical practice have raised the prospect of data-driven clinical decision making when addressing the issues of drug-drug interactions and genetic polymorphisms in metabolizing enzymes. Inhibition of metabolizing enzymes in drug interactions can lead to genotype-phenotype discrepancies (phenoconversion) that reduce the relevance of individual pharmacogenetic information.

AREAS COVERED: The aim of this review is to provide an overview on existing models of phenoconversion and we discuss how phenoconversion models may be developed to estimate joint drug-interactions and genetic effects. Based on a literature search in PubMed, Google Scholar and reference lists from review articles, we provide an overview on the current models of phenoconversion. The currently applied phenoconversion models are presented, and discussed to predict effects of drug-drug interactions while accounting for the pharmacogenetic status of patients.

EXPERT OPINION: While pharmacogenetic dose recommendations alone are most relevant for rare and extreme genotypes, phenoconversion may increase the prevalence of these phenotypes. Therefore, in polypharmacy conditions, phenoconversion assessment is especially important for personalized drug therapy.

PMID:39791881 | DOI:10.1080/17425255.2025.2451440