Abstract Objectives To evaluate the impact of the TNF-α promoter SNP -308G/A on therapeutic response, serum drug levels, and immunogenicity of TNF inhibitors in chronic inflammatory rheumatic diseases. Methods This cross-sectional, multicentric study included 73 patients: 32 with rheumatoid arthritis (RA) and 41 with spondyloarthritis (SpA). Serum drug levels (SDL) and anti-drug antibodies (ADA) were quantified by ELISA (Promonitor ® ). Genotyping for SNP -308 was performed via PCR-RFLP. Therapeutic response was assessed at 6 months using delta DAS28 and EULAR response in RA and delta BASDAI, BASDAI20 and BASDAI50 responses in SpA patients. Results In RA, the heterozygous G/A genotype was significantly associated with a greater reduction in median DAS28 compared to G/G (p=0.039) and a higher proportion of good EULAR responders (p=0.154). In SpA, G/A carriers showed larger decreases in BASDAI scores though differences were not statistically significant. Across both diseases, the G/A genotype was associated with significantly higher median serum drug levels (p=0.032). No association was observed between SNP -308G/A and ADA positivity. Conclusions The TNF-α -308G/A polymorphism may be a predictive marker of TNF inhibitor efficacy in RA, potentially influencing serum drug levels while immunogenicity appears unaffected. Larger prospective studies are needed to confirm these findings and explore additional determinants of TNF inhibitor response.
OBJECTIVES:Withania somnifera (WS) is known for its adaptogenic benefits; however, its beneficial effects in neurodegenerative diseases have not been fully explored. MicroRNAs (miRNAs) are small noncoding RNAs whose role(s) in modulating the effects of WS in neurodegeneration are yet unknown. This study aimed to investigate the impact of WS on miRNA expression in the SK-N-SH human neuroblastoma cell line. METHODS:We employed high-throughput sequencing to identify miRNAs with altered expression following dose-dependent and temporal treatment with WS. RESULTS:Our findings revealed that miRNA expression profiles were significantly altered in WS-treated cells. In the dose comparison (100 μg/mL vs. 50 μg/mL), 21 miRNAs were modulated at 3 h (18 upregulated and 3 downregulated), whereas 7 miRNAs were modulated at 9 h (3 upregulated and 4 downregulated). In the temporal comparison (9 h vs. 3 h), 9 miRNAs were modulated at 50 μg/mL (6 upregulated and 3 downregulated), whereas 30 miRNAs were modulated at 100 μg/mL (4 upregulated and 26 downregulated). Bioinformatics analyses, including target prediction and functional enrichment, revealed that these WS-modulated differentially expressed miRNAs were significantly enriched in neurodegenerative, apoptotic, and inflammatory pathways. Finally, 51 novel miRNAs were identified post-WS treatment. CONCLUSIONS:Taken together, our results indicate that WS may be beneficial in neurodegenerative disease and healthy aging by modulating noncoding miRNAs.
Allergic diseases are common among women of reproductive age, which necessitates the use of antihistamine therapy during pregnancy while ensuring safety for both the mother and the foetus. The study aimed to determine the safety profile, pharmacological characteristics, and clinical consequences of antihistamine use during pregnancy for the maternal-foetal system. A systematic review of scientific publications for the period 2020-2025 was carried out using the PRISMA methodology with a search in five international databases, which allowed us to select 45 relevant sources analyzing pathophysiology, pharmacology, and clinical consequences. It has been established that maternal immunoglobulins of class E are transported across the placental barrier, where they may sensitise foetal mast cells in utero. Hormonal changes during pregnancy induce polarisation of the immune response towards Th2 with progressive suppression of eosinophils by 17-22 % in the second trimester and by 20-42 % in the third trimester. Population cohort studies covering more than 1.2 million pregnancies have found no statistically significant associations between the use of second-generation antihistamines and major congenital malformations, spontaneous abortions or premature births. Physiological changes during pregnancy modify the pharmacokinetic parameters of drugs, reducing plasma protein concentrations by 20-40 %, However, cetirizine and loratadine demonstrate a favourable safety profile based on data from more than 186,000 exposures in Scandinavian registries, and the relative infant dose remains below the 5 % safety threshold. The findings support the use of second-generation antihistamines as first-line therapy for allergic diseases in pregnancy and provide an evidence base for selecting safe pharmacological agents at different gestational stages.
OBJECTIVES:Ecstasy is commonly abused due to entactogenic effects. Although our previous studies on isolated perfused rat model confirmed inhibition of CYP2D6 by MDMA, the time for enzyme recovery was different when mirtazapine and tramadol were used as substrates. Therefore, present study intended to investigate CYP2D6 inhibition by MDMA using dextromethorphan as a well-known probe. Two different concentrations of dextromethorphan were used at therapeutic and saturated level to clarify observations. METHODS:Thirty-two rats were divided into two groups (dextromethorphan concentration: 2 µM or 300 µM). Each group was divided into four subgroups. Except for control, three treatment subgroups received a single dose of MDMA (1 mg/kg) 1 h, 1 week, and 1 month before liver perfusion, respectively. RESULTS:Mean metabolic ratio using therapeutic dextromethorphan concentration showed a statistically significant decrease only in the 1-hour group compared to control. The results of the mean metabolic ratio using the saturated concentration showed a reduction in all treatment groups (p-value<0.05). CONCLUSIONS:It can be concluded that the isoenzyme behavior can be completely different using therapeutic vs. saturated probe concentrations. The best explanation for the duality observed in metabolic behavior seems to be the dependence of the metabolite on enzymatic pathway.
INTRODUCTION:This study was conducted to assess the current state of issues related to AR to anaesthetics used in surgical procedures. CONTENTS:A literature review of scientific publications in allergology and anaesthesiology was performed, evaluating the allergenic profile of modern anaesthetics and analysing approaches to preventing AR during surgery. SUMMARY:Currently, the most commonly used local anaesthetics are amides, including lidocaine, bupivacaine, articaine, mepivacaine, ropivacaine, and levobupivacaine. These are considered safer in terms of allergenicity compared to their ester-based predecessors - novocaine, benzocaine, and tetracaine - as their metabolites rarely act as allergens. Among general anaesthetics, intravenous agents such as propofol, midazolam, etomidate, and ketamine, as well as inhalational agents including sevoflurane, isoflurane, desflurane, and xenon, are widely used. These are generally safer than their predecessor, thiopental, with xenon currently exhibiting the highest safety profile due to its inert chemical properties. Muscle relaxants have the highest allergenic potential, as their mechanism of action - blocking acetylcholine receptors - can lead to cell damage and the release of immune-stimulating substances. The only representative of depolarising muscle relaxants is succinylcholine, while non-depolarising agents include atracurium, cisatracurium, vecuronium, rocuronium, pancuronium, and mivacurium. OUTLOOK:Preventive measures to reduce the risk of AR include: a detailed patient history and diagnostic testing using skin tests, provocation tests, and/or blood tests for Immunoglobulin E (IgE); replacement of the allergenic drug with a safer alternative if an allergy is confirmed; close monitoring for allergic manifestations during surgery, with professional preparedness for resuscitation in cases of anaphylaxis; postoperative patient monitoring to detect potential delayed AR; documentation of all AR for future reference. The findings of this study may be applied in clinical practice to mitigate the risks of AR associated with anaesthetic use during surgical interventions.
OBJECTIVES:Very low birth weight (VLBW) infants are at disproportionately high risk for neonatal seizures, yet optimal first-line antiseizure medication (ASM) strategies in this vulnerable population remain a matter of debate. Over the past decade, levetiracetam (LEV) has emerged as a promising alternative to phenobarbital (PB), driven by growing concerns over PB's limited efficacy and potential neurotoxic effects. METHODS:This retrospective cohort study analyzed medical records of VLBW infants treated for seizures at our Neonatal Intensive Care Unit from 2013 to 2023. We compared the efficacy and safety of LEV and PB as initial antiepileptic treatments. Data on gestational age, birth weight, type of seizures, electroencephalogram findings, and treatment outcomes were meticulously collected and analyzed. RESULTS:The study included 103 VLBW infants (mean gestational age 26.17±2.31 weeks); 27 received LEV and 76 received PB. Baseline demographic and clinical characteristics were comparable between the two groups. Although the LEV group had a higher proportion of infants with severe intraventricular hemorrhage and necrotizing enterocolitis indicating a potentially more critical baseline, these differences were not statistically significant. The primary outcome revealed that significantly fewer infants in the LEV group were unresponsive to initial treatment compared to the PB group (14.8 vs. 56.6 %; p<0.001). Furthermore, lower gestational age was identified as a significant risk factor for PB unresponsiveness. CONCLUSIONS:This study supports that LEV is more successful in clinical seizure control compared to PB as the first choice in ASM selection in VLBW. If our study results are supported by randomized controlled prospective studies, LEV, with its potentially fewer side effects, could be included in clinical algorithms as the first-choice ASM especially for VLBW.
OBJECTIVES:A growing set of drugs includes a pharmacogenetic biomarker as a requirement before prescription. This study aims to determine the frequency of allelic variants with functional repercussions in clinically relevant pharmacogenes and its relation with genomic ancestry in Cuban individuals. METHODS:10 single nucleotide variants (SNVs) across eight genes, included in the list of genetic variants required for the prescription of warfarin, tacrolimus, azathioprine, simvastatin, carbamazepine, abacavir and clopidogrel were analyzed. From genotyping in 948 Cuban individuals, population frequencies and Hardy-Weinberg equilibrium assessment were determined using PLINK v1.9. As a result of the ADMIXTURE analysis, previously performed on this sample, the relationship with the individual proportion of contribution of European, African, Native American and Asian ancestry was evaluated. RESULTS:Minor allele frequencies (MAFs) ranged from 0.0216 to 0.2781. Hardy-Weinberg equilibrium (HWE) deviations in three variants (CYP2C9 rs1799853, HLA-A rs1061235, SLCO1B1 rs4149056) were identified. Among individuals presenting the SNVs CYP2C9 rs1799853, CYP4F2 rs2108622, SLCO1B1 rs4149056, HLA-B rs2395029, the average European ancestry was higher; in contrast, individuals with the variant CYP3A5 rs10264272 presented higher African ancestry. CONCLUSIONS:The variability in the analysis of each included allele, is representative of the genetic heterogeneity of the Cuban population and provides a remarkable example of diversity among populations.
OBJECTIVES:To evaluate whether international decisions to withdraw medicines for safety, efficacy, or commercial reasons were reflected in the regulatory actions of Ecuador, Colombia, and Peru. METHODS:A retrospective, descriptive, cross-sectional analysis identified active pharmaceutical ingredients (APIs) withdrawn globally by Stringent Regulatory Authorities (SRAs) between January 1, 2014, and June 30, 2025. Data were obtained from published SRA communications and verified in national regulatory databases - ARCSA (Ecuador), INVIMA (Colombia), and DIGEMID (Peru) - to determine current marketing status. APIs were categorized as never registered (no evidence in current or archival databases), previously registered (formally canceled/suspended with a safe of efficacy rationale), previously registered (authorization expired without an explicit safety rationale), or currently registered (active marketing authorization). RESULTS:Fifty-three APIs were withdrawn internationally, predominantly for safety concerns (69.81 %), followed by lack of efficacy (22.64 %) and manufacturer decisions (7.55 %). The European Medicines Agency issued most withdrawals, particularly for oncologic and hormonal agents. Despite these actions, Ecuador retained 16.98 % of withdrawn APIs on its market, Peru 7.55 %, and Colombia 7.55 %. Persisting products included modified-release paracetamol, hydroxyethyl starch, and ulipristal 5 mg - drugs associated with hepatotoxicity or fatal adverse events. Regulatory databases often list expired or active authorizations without public withdrawal notices. CONCLUSIONS:Substantial misalignment persists between international and Andean regulatory decisions. The continued regulatory authorization of withdrawn medicines highlights weaknesses in pharmacovigilance and transparency, underscoring the urgent need for regional harmonization and public disclosure of regulatory actions.
OBJECTIVES:Clinical relevance of CYP2C19 genetic polymorphisms in real-world patient populations requires further investigation. This study aimed to determine the prevalence of CYP2C19 genetic variants in patients with GORD showing resistance to PPI therapy and possible clinical implications. METHODS:Patients with GORD and documented PPI resistance were identified from ambulatory reflux monitoring and endoscopy databases. EDTA blood samples were obtained for CYP2C19 genotyping using real-time polymerase chain reaction and reverse hybridisation. Genotypes (phenotypes) were categorised into: *1/*1 (normal metabolisers, NMs), *1/*17 (rapid metabolisers, RMs), *17/*17 (ultra-rapid metabolisers, UMs), *1/*2, *2/*17 (intermediate metabolisers, IMs), *2/*2 (poor metabolisers, PMs). RESULTS:Fifty patients were assessed (49 European ancestry, 28 male, modal age 50-59 years). Predominant resistance patterns included reflux hypersensitivity (n=19) and persistent oesophagitis (n=17). PPI therapy included esomeprazole (n=26), omeprazole (n=22), lansoprazole (n=2). Genotyping identified 26 NMs (52 %), 8 RMs (16 %), 14 IMs (28 %), 2 PMs (4 %); no UMs were identified. CONCLUSIONS:Findings from this preliminary study indicate a higher frequency of NMs and RMs compared to IMs and PMs in this PPI-resistant cohort with GORD. Most resistance was observed to the second-generation PPI esomeprazole. A limitation was the lack of a control group comprising PPI-sensitive patients.
OBJECTIVES:Allergic reactions to muscle relaxants are a major cause of perioperative anaphylaxis. This study aimed to evaluate how plasma concentrations of muscle relaxants, genetic predispositions, and immunometabolic changes influence the risk and severity of hypersensitivity reactions to improve diagnostic accuracy and support personalised perioperative management. METHODS:A total of 120 adult patients undergoing general anaesthesia were examined using intradermal testing, ELISA-based assays for specific IgE, basophil activation tests, cytokine profiling, plasma drug concentration measurements (HPLC-MS), molecular genetic analysis of IL-4 and IL-13 polymorphisms, and proton magnetic resonance spectroscopy for metabolic profiling. A control group (n=60) underwent parallel testing. Statistical evaluation included correlation analysis, logistic regression, and ROC curve assessment. RESULTS:Positive allergic reactions were observed in 15.8 % of patients, most commonly to atracurium (9.2 %). Patients with positive reactions showed significantly higher plasma concentrations of atracurium (2.8 ± 0.4 μg/mL vs. 1.7 ± 0.3 μg/mL; p<0.01). IL-4 (CC) and IL-13 (AA) genotypes increased the risk of hypersensitivity (OR 3.2 and 2.8, respectively), while their combination markedly elevated the likelihood of severe reactions (OR 5.6). Elevated IL-4, IL-6, and TNF-α levels correlated with clinical severity. Metabolic profiling revealed increased lactate, acetate, and pyruvate in allergic patients, indicating systemic inflammatory and anaerobic metabolic responses. ROC analysis confirmed high predictive accuracy for atracurium concentration (AUC=0.82) and genetic markers (AUC=0.79). CONCLUSIONS:Allergic reactions to muscle relaxants are strongly influenced by drug concentration, genetic susceptibility, and metabolic responses. Combined pharmacokinetic, immunological, and genetic assessment may significantly enhance preoperative risk stratification and support personalised anaesthetic management to improve patient safety.
OBJECTIVES:Chronic migraine is a prevalent and disabling neurological disorder affecting 1-3 % of the global population. Ancient Unani physicians have described herbal liniment ('Ṭilā) as a treatment modality for chronic migraine. This study aimed to evaluate its efficacy in managing the condition. METHODS:A randomized controlled trial was conducted on 36 patients with chronic migraine. Participants were divided into two groups: the test group (n=24), which received herbal liniment applied locally once daily for 15 days, and the control group (n=12), which underwent transcutaneous electrical nerve stimulation (TENS) for 30 min daily, 5 days a week, over 2 weeks. Outcomes were measured using the Visual Analogue Scale (VAS), headache frequency, and the Migraine Disability Assessment Scale (MIDAS) on days 15, 30, 60, and 90. RESULTS:Both groups showed significant improvement within the groups in headache frequency (p<0.0001). The test group demonstrated greater effectiveness, with larger reductions in headache frequency (mean difference 39.63; p<0.0001), VAS (mean difference 3.96; p<0.001), and MIDAS (mean difference 2.25; p=0.003). CONCLUSIONS:Herbal liniment effectively reduced migraine frequency, intensity, and disability. Larger studies are needed to validate these findings and assess long-term outcomes.
OBJECTIVES:Warfarin resistance represents a rare yet clinically significant challenge, especially among patients with mechanical heart valves. It may result from either hereditary or acquired factors. CASE PRESENTATION:A 27-year-old male patient with a history of aortic and mitral valve replacement was followed with subtherapeutic International Normalized Ratio (INR) of 1.8-2.0 despite receiving 20 mg/day of warfarin. He was hospitalized for evaluation, and potential acquired causes of warfarin resistance were excluded. The patient was discharged with a plan for close INR monitoring. Following the initiation of lorazepam and olanzapine for a comorbid psychiatric condition, he re-presented with bleeding manifestations due to warfarin overdose. Notably, his apparent warfarin resistance resolved after the addition of these medications, and he has since been maintained within the therapeutic INR range on a stable warfarin dose of 5 mg/day. CONCLUSIONS:Warfarin is known to interact with numerous medications, and new drug interactions continue to be reported in the literature. Although no major interactions with lorazepam or olanzapine have been previously documented, in this case the concomitant initiation of these agents appeared to overcome warfarin resistance. This clinical course was remarkable for the apparent resolution of warfarin resistance, raising the possibility of underlying pharmacologic interactions.
BACKGROUND:Selinum is an important genus in the Apiaceae family, known for its essential oil-bearing medicinal properties. Selinum vaginatum C. B. Clarke and Ligusticopsis wallichiana (DC.) Pimenov & Kljuykov (Syn. Selinum wallichianum (DC.) Raizada & H. O. Saxena and Selinum tenuifolium Wall. ex DC.) are the two important species found in Himachal Pradesh, India. CONTENT:The primary objective of this review is to present an updated report on the phytochemistry, traditional knowledge, and pharmacological profile of two species of the genus Selinum that are found in the Western Himalayas. SUMMARY:The genus Selinum is commonly referred to as Bhutakeshi or Bhootkeshi. Strong evidence supports Selinum's claims for its traditional ethnomedical importance and is used to treat cardiovascular diseases, asthma, toothache, mental disorders and diabetes. It is also used as an insect repellent and in magico-religious practices. The plant has antioxidant, anti-inflammatory, anticancer, anticonvulsant, and antimicrobial activities. The plant is rich in phenols, flavonoids, alkaloids, and terpenoids that contribute to its bioactivities. OUTLOOK:This review outlines the important phytochemicals, traditional uses, and potential pharmacological properties of Selinum species. Further investigation is needed to elucidate the mechanistic importance of its bioactive components in drug development processes and to investigate the therapeutic potential at the clinical level.
OBJECTIVES:Defined by their unique covalently closed loop, circular RNAs (circRNAs) are a specific class of noncoding RNAs known for their stability and resilience against degradation. They act as microRNA sponges, transcriptional regulators, and modulators of protein interactions. Withania somnifera (WS), a prominent member of the Solanaceae family, is renowned for its anti-oxidative and neuroprotective properties. Although circRNAs are recognized as critical regulators in neurological disorders, their putative roles in eliciting the health-beneficial effects of WS, also known as Ashwagandha, are still unexplored. METHODS:This study investigates WS-modulated global circRNA expression profiles in the SK-N-SH human neuroblastoma cell line, a widely used model for brain-related diseases. We conducted whole genome circRNA profiling using sequencing to identify differentially expressed circRNAs upon WS treatment. RESULTS:A total of 26,489 circRNAs were detected, out of which 1,515 were novel. Dose-dependent and temporal differential gene expression analysis found 26 upregulated and 20 downregulated circRNAs which were linked to pathways relevant to neuroinflammation, synaptic plasticity and neuronal survival through functional and pathway enrichment analysis. CONCLUSIONS:This study sheds light on the regulatory roles of circRNAs in WS's therapeutic effects, suggesting that modulating circRNA expression may be a key mechanism by which it exerts its benefits. These findings open new avenues for WS-based therapeutic strategies for brain-related diseases, thereby highlighting the therapeutic utility of circRNAs in neurological contexts.
OBJECTIVES:The increasing resistance of human infections to pharmaceutical treatments represents a critical global health challenge. Traditional herbs may complement modern antibacterial strategies. This study investigates the antimicrobial, antioxidant, and immunomodulatory properties of Eugenol extracted from Syzygium aromaticum. METHODS:The essential oil was achieved through hydro distillation and analyzed using HPLC. Antioxidant capabilities were assessed using the DPPH radical scavenging assay and reducing power. MTT assays revealed the viability percentages of A549 and MRC5 cell lines after 48 h of exposure to methanolic extract and valerianic acid. Minimum inhibitory concentration (MIC) and broth microdilution methods were utilized to test antibiotic activity against Staphylococcus aureus, Escherichia coli, and Candida albicans. Finally, the essential oil (average concentration 13.1 % ± 0.23, with major components Eugenol, β-caryophyllene, and Eugenol Acetate) was orally administered to rats for 14 days. In vivo safety and immunomodulatory effects were assessed through histopathological, hematological, and hepatic enzyme analyses, as well as cytokine profiling. RESULTS:The essential oil, rich in Eugenol, β-caryophyllene, and Eugenol acetate, demonstrated strong antioxidant activity. It exhibited significant antimicrobial effects at concentrations≥5 mg/mL, with inhibition zones comparable to standard antibiotics. Cytotoxicity remained low, and in vivo analysis revealed no adverse effects. The extract also increased IFN-γ and IL-4 levels, indicating immunomodulatory potential. CONCLUSIONS:The study indicated an immunomodulatory impact by increasing IFN-γ and IL-4 levels, with no negative effects on hepatic enzymes, hematological parameters, or histopathology. In summary, this research demonstrates that Eugenol, even at low concentrations, exhibits promising antioxidant and antimicrobial activities against common pathogens.
The identification of genetic markers that will enable accurate diagnosis and prediction of the therapy outcome is a crucial step in managing rheumatologic and autoimmune diseases. Low-dose methotrexate is a mainstay therapeutic agent for treatment. The objective of this review is to summarize the data on candidate single nucleotide polymorphisms in methylenetetrahydrofolate reductase (MTHFR) and solute carrier family 19 member 1 (SLC19A1) genes involved in methotrexate pathways. Over the past decade, several functional polymorphisms affecting methylenetetrahydrofolate reductase activity have been studied in the context of low-dose methotrexate therapy. The most frequently investigated polymorphisms are rs1801133 (c.665C>T) and rs1801131 (c.1286A>C) in MTHFR gene and rs1051266 (c.80A>G) in SLC19A1 gene. Although the effects of these polymorphisms are remaining unclear, several studies have shown association with adverse effect while fewer studies have demonstrated association with remission or positive response to methotrexate. However, there is scarcity research in Latin American population assessing the influence of genetic variants in the pharmacokinetics and pharmacodynamics of methotrexate in the context of interethnic admixture. There is an urgent need of to expand these studies and to support the development of clinical pharmacogenomics guidelines.
OBJECTIVES:Pharmacogenomics (PGx) testing optimizes drug efficacy and minimizes adverse effects, yet its implementation in Iraq remains limited. This study assessed Iraqi pharmacists' attitudes toward PGx testing to identify gaps in education and clinical readiness. METHODS:A cross-sectional survey of 99 Iraqi pharmacists was conducted (June-August 2020). The 20-item questionnaire evaluated demographics, PGx education exposure, attitudes, and self-reported competence using a three-point Likert scale. Data were analyzed descriptively via SPSS. RESULTS:Most participants were young (83 % aged 21-30), held bachelor's degrees (87.88 %), and supported PGx integration into curricula (80.81 %). While 95 % believed pharmacists should possess PGx knowledge, self-reported competency was low (35-54 %). CONCLUSIONS:Despite strong support for PGx, limited educational exposure and low confidence in applying PGx testing highlight the need for curriculum enhancements and targeted training programs in Iraq. Iraqi pharmacists recognize PGx's clinical value but require further education to bridge competence gaps. Policymakers should prioritize PGx training to facilitate implementation.
The ESR1 gene encodes estrogen receptor alpha (ERα), whose central role in breast tumorigenesis has supported the development of endocrine therapies, including selective estrogen receptor modulators (SERMs) and aromatase inhibitors (AIs). Despite their proven efficacy, resistance, relapse, and treatment-limiting toxicity remain frequent, underscoring interindividual and interpopulation variability in therapeutic outcomes. Allelic diversity within ESR1 is a key determinant of these differences, as variant frequencies and distributions vary substantially across populations and ethnic groups. Associating ESR1 variants with genomic ancestry can help anticipate variability in drug response, thereby reducing adverse events and facilitating the clinical implementation of pharmacogenetics. Investigating population-specific differences that shape drug efficacy and toxicity not only generates evidence for groups historically underrepresented in genomic studies but also enhances the equity and global applicability of personalized medicine. In conclusion, genetic variation in ESR1 may modulate both the efficacy and safety of breast cancer therapies. Understanding the genetic diversity of populations worldwide is therefore essential for minimizing adverse effects, improving treatment outcomes, and advancing the implementation of pharmacogenetics in clinical practice.
