Fluoropyrimidines are among the most useful drugs in oncology with an established record of efficacy and safety. A minority of oncology patients bear genetic variants with reduced activity of the main enzyme catabolizing these drugs, dihydropyrimidine dehydrogenase (DPYD) and may be prone to severe or even lethal adverse effects. We reviewed the records of gastrointestinal and breast cancer patients treated in our cancer center for the identification of cases that had DPYD genetic testing for variants and received treatment with fluoropyrimidines. The records of patients fulfilling these criteria were retrieved, and the prevalence of the different variants and their clinical implications and outcomes were recorded. The overall prevalence of four common DPYD variants was 7.3% (10 of 137 patients). Most prevalent variant was the haplotype HapB3 (five patients, 3.6%), followed by the DPYD p.D949V variant (3 patients, 2.2%), while one patient each (0.7%) had the two null variants DPYD*2A and DPYD*13. A sizable minority of oncology patients bear variants of DPYD with reduced activity and may be at increased risk of fluoropyrimidine toxicities if treated at full doses. However, variability within the same genotype exists.

This systematic review and meta-analysis aimed to investigate the association between ABCG2 polymorphisms and allopurinol response in gout patients. A comprehensive search of Scopus, PubMed, Web of Science, EBSCOhost, and the Clinical Pharmacogenomic Resource was conducted for observational studies up to May 2025. Two authors independently screened studies, extracted data, and assessed study quality using the Newcastle-Ottawa Scale. Pooled odds ratios with 95% confidence intervals were calculated using a random-effects model across codominant, dominant, and recessive genetic models. Statistical heterogeneity was evaluated using the I2 statistic, and sensitivity analyses were performed. Six studies met the inclusion criteria for the review, and five were included in the meta-analysis. A significant association was observed between rs2231142 with poor allopurinol response, but not rs10011796. Sensitivity analyses confirmed the robustness of the findings for rs2231142. The findings suggest that ABCG2 rs2231142 influences allopurinol response. These results underscore the potential of rs2231142 as a predictive genetic marker for allopurinol efficacy and may inform the development of pharmacogenomic guidelines for gout management.This systematic review and meta-analysis was not registered in any protocol registry.

Screening for dihydropyrimidine dehydrogenase (DPD) deficiency has been recommended by both the European Medicines Agency (EMA) and the U.S. Food and Drug Administration (FDA) to prevent fluoropyrimidine toxicity. Depending on national guidelines, it relies on phenotyping or variants genotyping. We assessed the benefit of DPYD sequencing to identify unreported variants that may alter enzyme function. We retrospectively analyzed DPYD next-generation sequencing results obtained from 1145 individuals at Limoges University Hospital between November 2020 and July 2025. Fifty-one DPYD variants were identified including several rare variants and copy-number variation (CNV) that are not addressed in current guidelines. Four were common (MAF ≥ 5%), 6 rare (MAF ≥ 0.5% and < 5%) and 41 very rare (MAF < 0.5%). Eight showed a Clinical Pharmacogenetics Implementation Consortium (CPIC) score indicative of decreased or null activity; 12 were classified normal-function allele, and 31had no CPIC annotation. In this cohort, 73 (6.3%) individuals carried at least one decreased-function allele, while 28 (2.4%) had potentially damaging rare or structural variants (including 5 CNVs). NGS analysis enables the identification of DPYD rare or structural variants with potential functional impact, thereby improving the genetic assessment of DPD deficiency.

Anti-tuberculosis drug-induced liver injury (AT-DILI) is one of the significant adverse effects of first-line tuberculosis therapy, frequently resulting in treatment discontinuation. Genetic polymorphisms in N-acetyltransferase 2 (NAT2), a key enzyme in the metabolism of isoniazid (an anti-TB drug), are suggested to influence AT-DILI susceptibility. A meta-analysis of published studies was conducted to evaluate the association between NAT2 polymorphisms and the risk of AT-DILI. Literature searches were conducted in PubMed, Web of Science, Wiley, ScienceDirect, and Medline up to December 2024. A total of 48 studies comprising 11,035 patients were included. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Subgroup analyses were conducted based on region, study design, genotyping method, hepatotoxicity definitions, and NAT2 genetic variants. Heterogeneity, publication bias, quality assessment, and sensitivity analysis were assessed using the I2 statistic, Egger's test, the Newcastle-Ottawa Scale (NOS), and the leave-one-out method, respectively. Slow acetylator genotypes were significantly associated with an increased risk of AT-DILI (pooled OR = 3.02; 95% CI = 2.50-3.64; p < 0.001). Moderate heterogeneity was observed (I2 = 58.74%). No significant publication bias was observed (p = 0.199). NAT2 acetylator status was significantly associated with the likelihood of experiencing hepatotoxicity related to anti-tuberculosis drugs.

Metoprolol, a β1-selective blocker, is widely used for treating cardiovascular and non-cardiovascular conditions. Its pharmacokinetics (PK) and pharmacodynamics (PD) vary significantly between individuals, in part due to CYP2D6 genetic polymorphisms. Co-administration of CYP2D6 inhibitors can lead to phenotype-genotype discordance, known as phenoconversion, resulting in clinically significant changes in metoprolol exposure and response. This review examines studies of the combined impact of CYP2D6 genotype and inhibitor use on metoprolol PK and PD. A literature search of PubMed, Embase, and Scopus identified 17 relevant clinical studies. Strong inhibitors such as paroxetine and fluoxetine increased metoprolol exposure by up to 8-fold and induced phenoconversion in extensive metabolizers. Moderate inhibitors, including mirabegron and amiodarone, increased metoprolol exposure by 2- to 3-fold, particularly in those with high baseline CYP2D6 activity. These inhibitors also reduced heart rate and blood pressure, mimicking the response seen in poor metabolizers. Weak inhibitors caused minimal PK changes without notable PD effects. Severe adverse drug reactions, including bradycardia and hypotension, occurred with strong inhibitors, especially in patients with cardiovascular disease and reduced CYP2D6 function. CYP2D6 phenoconversion is a clinically important but often overlooked contributor to metoprolol response variability. Incorporating phenoconversion into clinical practice can lead to more effective pharmacotherapy with metoprolol.

Glaucoma is a chronic, degenerative eye disease for which personalized diagnostic and therapeutic biomarkers are still lacking. Precision medicine offers a promising strategy to improve glaucoma management, and pharmacogenomics may play a key role in optimizing treatment response, minimizing side effects, and enhancing adherence. Advances in genetics have introduced potential tools such as polygenic risk scores (PRS) for adult-onset glaucoma and CRISPR/Cas9 for early-onset monogenic forms. Although still in its early stages, pharmacogenetic research in glaucoma has identified several genetic variants that may influence drug efficacy and security. Notably, single nucleotide polymorphisms in genes such as PTGFR, ADRB2 and CYP2D6 have been associated with varied responses to beta-blockers and prostaglandin analogues. Other candidate genes include ABCB1, SLCO2A1, AFAP1, and ADRB1, though findings remain preliminary. Despite the appeal of genetically guided therapy, broader implementation in clinical practice requires larger, multicenter validation studies, functional analysis of variants, and consensus on actionable biomarkers. Until then, early diagnosis, adherence, and timely treatment remain the pillars of glaucoma care. This narrative review provides an updated overview of the current evidence, knowledge gaps, and future directions in the pharmacogenomics of glaucoma.

To examine whether patients with depression or chronic/acute pain understand the results of pharmacogenomic testing they had done as part of clinical research. Semi-structured interviews were conducted with 45 patients who underwent pharmacogenomic testing and subsequently received their testing results by mail. These interviews assessed whether participants were aware that they had testing, how this testing impacted their current medications, and whether they grasped the future significance of this testing. A grounded theory approach was used to analyze this interview data. All of our participants were aware that they had underwent medical testing and 23 (51%) were aware that this testing was genetic and was used to guide medication management. Almost all of our participants believed it was important to share their results with future providers and 24 (53%) recognized that their results could impact future medication management. Thirteen (29%) participants stated that their results found medicines they should avoid and eight named specific medicines they believed should be avoided based on their results. Although our participants exhibited a general understanding of their pharmacogenomic results, we found that they lacked a sufficient understanding of how these results specifically impacted their current and future healthcare.

The present review explores the existing evidence on pharmacogenomic tests for prediction of lithium response in the treatment of bipolar disorder. We focused our research article on reports describing findings from genome-wide association studies, polygenic risk scores, and gene expression analyses associated with lithium response. We conducted a non-systematic review of studies from PubMed/Medline by using terms such as "pharmacogenomics," "GWAS," "gene expression," and "lithium response." Inclusion criteria focused on original research involving human subjects and assessing lithium response outcomes as well as in vitro studies. An extensive pearl-growing strategy was employed to further enlarge the scope of the piece by capitalizing on the knowledge of study authors on the subject. The observed results, albeit promising, remain preliminary in terms of clinical relevance. Machine learning combining genetic and clinical data appears associated with moderate success in predicting lithium responsiveness. Gene expression studies and genome-wide association studies have helped identify possible targets of lithium and have the potential to support target-specific drug research. Pharmacogenomics may support further discoveries in precision medicine further enlarging our understanding of the underlying mechanisms of lithium for its efficacy. However, clinical applications currently appear out of reach in the near future.

This scoping review explores the impact of genetic polymorphisms on the pharmacokinetics and treatment responses of mycophenolic acid (MPA), an immunosuppressant. The study includes 83 articles from 1226 original studies, focusing on transplantation (n=80) and autoimmune disorders (n=3). Genetic variants in uridine 5'-diphospho-glucuronosyltransferase (UGT1A9, UGT1A8 and UGT2B7) and transmembrane transporters (ABCC2, SLCO1B1, SLCO1B3 and ABCB1) significantly affected MPA's pharmacokinetics and susceptibility to its adverse effect. Whereas variants in several genes including UGT1A9, UGT2B7, IMPDH1 and IMPDH2 have been associated with a higher risk of transplant rejection. However, there is a lack of studies on MPA's impact on autoimmune disorders and limited research on the Asian population. The findings underscore the need for further research on MPA's impact across different populations and diseases, particularly among other Asian ethnic groups, to advance personalized medicine in MPA therapy.

Aim: The study aim was to determine caregiver interest and planned utilization of pharmacogenomic (PGx) results for their child with Prader-Willi syndrome. Methods: Caregivers consented to PGx testing for their child and completed a survey before receiving results. Results: Of all caregivers (n=48), 93.8% were highly interested in their child's upcoming PGx results. Most (97.9%) planned to share results with their child's medical providers. However, only 47.9% of caregivers were confident providers would utilize the PGx results. Conclusion: Caregivers are interested in utilizing PGx but are uncertain providers will use these results in their child's care. More information about provider comfort with PGx utilization is needed to understand how PGx education would benefit providers and ultimately patients with PGx results.