Pharmacogenomics Journal最新文献

{"title":"Using ChatGPT to predict the future of personalized medicine","authors":"George P. Patrinos, Negar Sarhangi, Behnaz Sarrami, Nazli Khodayari, Bagher Larijani, Mandana Hasanzad","doi":"10.1038/s41397-023-00316-9","DOIUrl":"10.1038/s41397-023-00316-9","url":null,"abstract":"Personalized medicine is a novel frontier in health care that is based on each person’s unique genetic makeup. It represents an exciting opportunity to improve the future of individualized health care for all individuals. Pharmacogenomics, as the main part of personalized medicine, aims to optimize and create a more targeted treatment approach based on genetic variations in drug response. It is predicted that future treatments will be algorithm-based instead of evidence-based that will consider a patient’s genetic, transcriptomic, proteomic, epigenetic, and lifestyle factors resulting in individualized medication. A generative pretrained transformer (GPT) is an artificial intelligence (AI) tool that generates language resembling human-like writing enabling users to engage in a manner that is practically identical to speaking with a human being. GPT’s predictive algorithms can respond to questions that have never been addressed. Chat Generative Pretrained Transformer (ChatGPT) is an AI chatbot’s advanced with conversational capabilities. In the present study, questions were asked from ChatGPT about the future of personalized medicine and pharmacogenomics. ChatGPT predicted both to be a promising approach with a bright future that holds great promises in improving patient outcomes and transforming the field of medicine. But it still has several limitations that need to be solved.","PeriodicalId":54624,"journal":{"name":"Pharmacogenomics Journal","volume":"23 6","pages":"178-184"},"PeriodicalIF":2.8,"publicationDate":"2023-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41168194","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The INGENIOUS trial: Impact of pharmacogenetic testing on adverse events in a pragmatic clinical trial","authors":"Michael T. Eadon, Marc B. Rosenman, Pengyue Zhang, Cathy R. Fulton, John T. Callaghan, Ann M. Holmes, Kenneth D. Levy, Samir K. Gupta, David M. Haas, Raj Vuppalanchi, Eric A. Benson, Rolf P. Kreutz, Emma M. Tillman, Tyler Shugg, Rebecca C. Pierson, Brandon T. Gufford, Victoria M. Pratt, Yong Zang, Zeruesenay Desta, Paul R. Dexter, Todd C. Skaar","doi":"10.1038/s41397-023-00315-w","DOIUrl":"10.1038/s41397-023-00315-w","url":null,"abstract":"Adverse drug events (ADEs) account for a significant mortality, morbidity, and cost burden. Pharmacogenetic testing has the potential to reduce ADEs and inefficacy. The objective of this INGENIOUS trial (NCT02297126) analysis was to determine whether conducting and reporting pharmacogenetic panel testing impacts ADE frequency. The trial was a pragmatic, randomized controlled clinical trial, adapted as a propensity matched analysis in individuals (N = 2612) receiving a new prescription for one or more of 26 pharmacogenetic-actionable drugs across a community safety-net and academic health system. The intervention was a pharmacogenetic testing panel for 26 drugs with dosage and selection recommendations returned to the health record. The primary outcome was occurrence of ADEs within 1 year, according to modified Common Terminology Criteria for Adverse Events (CTCAE). In the propensity-matched analysis, 16.1% of individuals experienced any ADE within 1-year. Serious ADEs (CTCAE level ≥ 3) occurred in 3.2% of individuals. When combining all 26 drugs, no significant difference was observed between the pharmacogenetic testing and control arms for any ADE (Odds ratio 0.96, 95% CI: 0.78–1.18), serious ADEs (OR: 0.91, 95% CI: 0.58–1.40), or mortality (OR: 0.60, 95% CI: 0.28–1.21). However, sub-group analyses revealed a reduction in serious ADEs and death in individuals who underwent pharmacogenotyping for aripiprazole and serotonin or serotonin-norepinephrine reuptake inhibitors (OR 0.34, 95% CI: 0.12–0.85). In conclusion, no change in overall ADEs was observed after pharmacogenetic testing. However, limitations incurred during INGENIOUS likely affected the results. Future studies may consider preemptive, rather than reactive, pharmacogenetic panel testing.","PeriodicalId":54624,"journal":{"name":"Pharmacogenomics Journal","volume":"23 6","pages":"169-177"},"PeriodicalIF":2.8,"publicationDate":"2023-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41397-023-00315-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10561330","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessment of clinically actionable pharmacogenetic markers to stratify anti-seizure medications","authors":"Debleena Guin, Yasha Hasija, Ritushree Kukreti","doi":"10.1038/s41397-023-00313-y","DOIUrl":"10.1038/s41397-023-00313-y","url":null,"abstract":"Epilepsy treatment is challenging due to heterogeneous syndromes, different seizure types and higher inter-individual variability. Identification of genetic variants predicting drug efficacy, tolerability and risk of adverse-effects for anti-seizure medications (ASMs) is essential. Here, we assessed the clinical actionability of known genetic variants, based on their functional and clinical significance and estimated their diagnostic predictability. We performed a systematic PubMed search to identify articles with pharmacogenomic (PGx) information for forty known ASMs. Functional annotation of the identified genetic variants was performed using different in silico tools, and their clinical significance was assessed using the American College of Medical Genetics (ACMG) guidelines for variant pathogenicity, level of evidence (LOE) from PharmGKB and the United States-Food and drug administration (US- FDA) drug labelling with PGx information. Diagnostic predictability of the replicated genetic variants was evaluated by calculating their accuracy. A total of 270 articles were retrieved with PGx evidence associated with 19 ASMs including 178 variants across 93 genes, classifying 26 genetic variants as benign/ likely benign, fourteen as drug response markers and three as risk factors for drug response. Only seventeen of these were replicated, with accuracy (up to 95%) in predicting PGx outcomes specific to six ASMs. Eight out of seventeen variants have FDA-approved PGx drug labelling for clinical implementation. Therefore, the remaining nine variants promise for potential clinical actionability and can be improvised with additional experimental evidence for clinical utility.","PeriodicalId":54624,"journal":{"name":"Pharmacogenomics Journal","volume":"23 6","pages":"149-160"},"PeriodicalIF":2.8,"publicationDate":"2023-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10078557","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genome-wide association study on pharmacological outcomes of musculoskeletal pain in UK Biobank","authors":"Song Li, Geert Poelmans, Regina L. M. van Boekel, Marieke J. H. Coenen","doi":"10.1038/s41397-023-00314-x","DOIUrl":"10.1038/s41397-023-00314-x","url":null,"abstract":"The pharmacological management of musculoskeletal pain starts with NSAIDs, followed by weak or strong opioids until the pain is under control. However, the treatment outcome is usually unsatisfying due to inter-individual differences. To investigate the genetic component of treatment outcome differences, we performed a genome-wide association study (GWAS) in ~23,000 participants with musculoskeletal pain from the UK Biobank. NSAID vs. opioid users were compared as a reflection of the treatment outcome of NSAIDs. We identified one genome-wide significant hit in chromosome 4 (rs549224715, P = 3.88 × 10−8). Suggestive significant (P < 1 × 10−6) loci were functionally annotated to 18 target genes, including four genes linked to neuropathic pain processes or musculoskeletal development. Pathway and network analyses identified immunity-related processes and a (putative) central role of EGFR. However, this study should be viewed as a first step to elucidate the genetic background of musculoskeletal pain treatment.","PeriodicalId":54624,"journal":{"name":"Pharmacogenomics Journal","volume":"23 6","pages":"161-168"},"PeriodicalIF":2.8,"publicationDate":"2023-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41397-023-00314-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10004994","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HLA-DQA1*05 and upstream variants of PPARGC1B are associated with infliximab persistence in Japanese Crohn’s disease patients","authors":"Fumiko Shimoda, Takeo Naito, Yoichi Kakuta, Yosuke Kawai, Katsushi Tokunaga, NCBN Controls WGS Consortium, Yusuke Shimoyama, Rintaro Moroi, Hisashi Shiga, Masao Nagasaki, Yoshitaka Kinouchi, Atsushi Masamune","doi":"10.1038/s41397-023-00312-z","DOIUrl":"10.1038/s41397-023-00312-z","url":null,"abstract":"Recently, the HLA-DQA1*05 (rs2097432) genetic variation has been reported to be linked to early infliximab (IFX) treatment failure in the Caucasian Crohn’s disease (CD) population, but that evidence is scarce in the Asian population. This study aimed to investigate the relationship between rs2097432 and the cumulative discontinuation-free time of IFX (IFX persistence) in 189 Japanese biologics-naive CD patients. We also performed a genome-wide association study (GWAS) to discover novel genetic predictors for IFX persistence. The C allele of rs2097432 significantly increased the risk of early discontinuation of IFX [Hazard ratio (HR) = 2.23 and P-value = 0.026]. In GWAS, one locus tagged by rs73277969, located upstream of PPARGC1B which attenuates macrophage-mediated inflammation, reached genome-wide significance (HR = 6.04 and P-value = 7.93E−9). Pathway analysis suggested association of signaling by PDGF and FCGR activation signaling with IFX persistence (P-value = 8.56E−5 and 5.80E−4, respectively).","PeriodicalId":54624,"journal":{"name":"Pharmacogenomics Journal","volume":"23 6","pages":"141-148"},"PeriodicalIF":2.8,"publicationDate":"2023-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41397-023-00312-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10203498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to: One year of experience with combined pharmacokinetic/pharmacogenetic monitoring of anti-TNF alpha agents: a retrospective study","authors":"Stefania Cheli, Diego Savino, Annalisa De Silvestri, Lorenzo Norsa, Naire Sansotta, Francesca Penagini, Dario Dilillo, Roberto Panceri, Dario Cattaneo, Emilio Clementi, Giovanna Zuin","doi":"10.1038/s41397-023-00311-0","DOIUrl":"10.1038/s41397-023-00311-0","url":null,"abstract":"","PeriodicalId":54624,"journal":{"name":"Pharmacogenomics Journal","volume":"23 5","pages":"140-140"},"PeriodicalIF":2.8,"publicationDate":"2023-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41397-023-00311-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10350382","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SLCO1B1*5 is protective against non-senile cataracts in cohort prescribed statins: analysis in a British-South Asian cohort","authors":"Emma F. Magavern, David A. van Heel, Genes & Health Research Team, Damian Smedley, Mark J. Caulfield","doi":"10.1038/s41397-023-00307-w","DOIUrl":"10.1038/s41397-023-00307-w","url":null,"abstract":"Reported association between statin use and cataract risk is controversial. The SLCO1B1 gene encodes a transport protein responsible for statin clearance. The aim of this study was to investigate a possible association between the SLCO1B1*5 reduced function variant and cataract risk in statin users of South Asian ethnicity. The Genes & Health cohort consists of British-Bangladeshi and British-Pakistani participants from East London, Manchester and Bradford, UK. SLCO1B1*5 genotype was assessed with the Illumina GSAMD-24v3-0-EA chip. Medication data from primary care health record linkage was used to compare those who had regularly used statins compared to those who had not. Multivariable logistic regression was used to test for association between statin use and cataracts, adjusting for population characteristics and potential confounders in 36,513 participants. Multivariable logistic regression was used to test association between SLCO1B1*5 heterozygotes or homozygotes and cataracts, in subgroups having been regularly prescribed statins versus not. Statins were prescribed to 35% (12,704) of participants (average age 41 years old, 45% male). Non-senile cataract was diagnosed in 5% (1686) of participants. An apparent association between statins and non-senile cataract (12% in statin users and 0.8% in non-statin users) was negated by inclusion of confounders. In those prescribed a statin, presence of the SLCO1B1*5 genotype was independently associated with a decreased risk of non-senile cataract (OR 0.7 (CI 0.5–0.9, p 0.007)). Our findings suggest that there is no independent association between statin use and non-senile cataract risk after adjusting for confounders. Among statin users, the SLCO1B1*5 genotype is associated with a 30% risk reduction of non-senile cataracts. Stratification of on-drug cohorts by validated pharmacogenomic variants is a useful tool to support or repudiate adverse drug events in observational cohorts.","PeriodicalId":54624,"journal":{"name":"Pharmacogenomics Journal","volume":"23 5","pages":"134-139"},"PeriodicalIF":2.8,"publicationDate":"2023-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10506906/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10663144","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between functional FCGR3A F158V and FCGR2A R131H polymorphisms and responsiveness to rituximab in patients with autoimmune diseases: a meta-analysis","authors":"Young Ho Lee, Gwan Gyu Song","doi":"10.1038/s41397-023-00308-9","DOIUrl":"10.1038/s41397-023-00308-9","url":null,"abstract":"To investigate the association between the functional Fc gamma receptor 3 A (FCGR3A) V158F and FCGR2A R131H polymorphisms and rituximab therapy in patients with autoimmune diseases. We searched the Medline, Embase, and Cochrane databases for relevant articles. We conducted a meta-analysis of the association between FCGR3A V158F and FCGR2A R131H polymorphisms and responsiveness to rituximab in patients with autoimmune diseases. Eleven studies, consisting of 661 responders and 267 non-responders for FCGR3A V158F polymorphism and 156 responders and 89 non-responders for FCGR2A R131H polymorphism, were included. The meta-analysis revealed a significant association between the FCGR3A V allele and responsiveness to rituximab (odds ratio [OR] = 1.600, 95% confidence interval [CI] = 1.268–2.018, P < 0.001). Furthermore, associations were found using the dominant and homozygous contrast models. Subgroup analysis showed an association between the FCGR3A V allele and responsiveness to rituximab in European, RA, ITP, small (<50) and large (≥50) groups, and short- (≤6 months) and long-term follow-up periods (≥6 months). These associations were also found in recessive, dominant or homozygous contrast models. Meta-analysis revealed no association between the FCGR2A R allele and responsiveness to rituximab (OR = 1.243, 95% CI = 0.825–1.873, P = 0.229). We demonstrated that the FCGR3A F158V polymorphism is associated with better responsiveness to rituximab therapy in patients with autoimmune diseases, indicating that individuals carrying the FCGR3A V allele will likely respond better to rituximab. However, FCGR2A R131H polymorphism was not associated with better response to rituximab.","PeriodicalId":54624,"journal":{"name":"Pharmacogenomics Journal","volume":"23 6","pages":"210-216"},"PeriodicalIF":2.8,"publicationDate":"2023-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9470995","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Knowledge and attitudes of medical and pharmacy students about pharmacogenomics: a systematic review and meta-analysis","authors":"Chen Li, Xiaona Su, Qidi Sun, Yi Huang","doi":"10.1038/s41397-023-00306-x","DOIUrl":"10.1038/s41397-023-00306-x","url":null,"abstract":"Pharmacogenomics (PGx) is rapidly growing branch of molecular genetics with high potentials to influence therapeutics. This review evaluates knowledge and attitudes of medical and pharmacy students about PGx. A literature search was conducted in electronic databases and studies were selected by following precise eligibility criteria. After quality assessment, studies were reviewed systematically, and meta-analyses of proportions were performed to estimate response rates of students. Fifteen studies (5509 students; 69% [95% confidence interval (CI): 60%, 77%] females) were included. Among students, 28% [95%CI: 12, 46] had adequate PGx knowledge; 65% [95%CI: 55, 75] were willing to have PGx test for their own risk assessment; 78% [95%CI: 71, 84] had intention to incorporate PGx in future practice; and 32% [95%CI: 21, 43] were satisfied with current PGx component of curriculum. Age, advanced year of educational program, and more time spent in PGx education were positively associated with PGx knowledge and positive attitudes.","PeriodicalId":54624,"journal":{"name":"Pharmacogenomics Journal","volume":"23 5","pages":"127-133"},"PeriodicalIF":2.8,"publicationDate":"2023-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10644876","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DNA polymerase gamma variants and hepatotoxicity during maintenance therapy of childhood acute lymphoblastic leukemia: is there a causal relationship?","authors":"Tekla Harju, Anri Hurme-Niiranen, Maria Suo-Palosaari, Stine Nygaard Nielsen, Reetta Hinttala, Kjeld Schmiegelow, Johanna Uusimaa, Arja Harila, Riitta Niinimäki","doi":"10.1038/s41397-023-00303-0","DOIUrl":"10.1038/s41397-023-00303-0","url":null,"abstract":"Hepatotoxicity is a frequent complication during maintenance therapy of acute lymphoblastic leukemia (ALL) with 6-mercaptopurine and methotrexate. Elevated levels of methylated 6-mercaptopurine metabolites (MeMP) are associated with hepatotoxicity. However, not all mechanisms are known that lead to liver failure in patients with ALL. Variants in the POLG gene, which encodes the catalytic subunit of mitochondrial DNA polymerase gamma (POLG1), have been related to drug-induced hepatotoxicity, for example, by sodium valproate. The association of common POLG variants with hepatotoxicity during maintenance therapy was studied in 34 patients with childhood ALL. Of the screened POLG variants, four different variants were detected in 12 patients. One patient developed severe hepatotoxicity without elevated MeMP levels and harbored a heterozygous POLG p.G517V variant, which was not found in the other patients.","PeriodicalId":54624,"journal":{"name":"Pharmacogenomics Journal","volume":"23 5","pages":"105-111"},"PeriodicalIF":2.8,"publicationDate":"2023-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10506908/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10289646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}