Pharmacogenomics and Personalized Medicine最新文献

{"title":"16S rRNA Gene Sequencing of Gut Microbiota in Rheumatoid Arthritis Treated with 99Tc-MDP","authors":"Zhaowei Huang, Changming Chen, Linlin Tan, Yi Ling, Wukai Ma, Jin-an Zhang","doi":"10.2147/pgpm.s451065","DOIUrl":"https://doi.org/10.2147/pgpm.s451065","url":null,"abstract":"","PeriodicalId":509088,"journal":{"name":"Pharmacogenomics and Personalized Medicine","volume":"9 9","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141133372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An Aging-Related lncRNA Signature Establishing for Breast Cancer Prognosis and Immunotherapy Responsiveness Prediction","authors":"Yanshijing Zhou, Zihui Yang, Hong Zeng","doi":"10.2147/pgpm.s450960","DOIUrl":"https://doi.org/10.2147/pgpm.s450960","url":null,"abstract":"","PeriodicalId":509088,"journal":{"name":"Pharmacogenomics and Personalized Medicine","volume":"26 12","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141136356","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Germline <i>PRDM1</i> Variant rs2185379 in Long-Term Recurrence-Free Survivors of Advanced Ovarian Cancer.","authors":"Takashi Mitamura,&nbsp;Tianyue Zhai,&nbsp;Kanako C Hatanaka,&nbsp;Yutaka Hatanaka,&nbsp;Toraji Amano,&nbsp;Lei Wang,&nbsp;Shinya Tanaka,&nbsp;Hidemichi Watari","doi":"10.2147/PGPM.S387120","DOIUrl":"https://doi.org/10.2147/PGPM.S387120","url":null,"abstract":"<p><strong>Purpose: </strong>To identify the germline genetic characteristics of long-term recurrence-free survivors that can be applied to establishing a new strategy for curing advanced cancer, we investigated the whole-genome single nucleotide variants of ovarian cancer patients.</p><p><strong>Patients and methods: </strong>DNA specimens were obtained from rare long-term recurrence-free survivors with FIGO stage III-IV ovarian cancer with no recurrence for 8-23 years after primary treatments for a whole-genome analysis of approximately 660,000 single nucleotide variants. We then established a mouse model with a notable gene alteration by CRISPR/Cas9 to confirm the biological role.</p><p><strong>Results: </strong>The long-term recurrence-free survivors more frequently had germline heterozygous variant rs2185379 of the <i>PRDM1</i> gene exon than patients with early recurrence (6.8-fold, P=0.013) and the general population. In the mouse model, primary intraperitoneal disseminated tumors of allograft ID8 were significantly smaller in the germline heterozygous rs2185379 group than in the wild-type group (57.4% decrease, P=0.008). Immunohistochemistry showed that the area of distribution of infiltrating T lymphocytes with positive CD8 staining was significantly increased in the germline heterozygous rs2185379 group in comparison to the wild-type group.</p><p><strong>Conclusion: </strong>Germline heterozygous rs2185379 in <i>PRDM1</i> is correlated with an excellent prognosis and can be used to establish a new strategy for treating advanced ovarian cancer.</p>","PeriodicalId":509088,"journal":{"name":"Pharmacogenomics and Personalized Medicine","volume":" ","pages":"977-984"},"PeriodicalIF":1.9,"publicationDate":"2022-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/92/0a/pgpm-15-977.PMC9719363.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35210812","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Utilization of Drugs with Pharmacogenetic Dosing Recommendations in Switzerland: A Descriptive Study Using the Helsana Database.","authors":"Nina L Wittwer,&nbsp;Christoph R Meier,&nbsp;Carola A Huber,&nbsp;Henriette E Meyer Zu Schwabedissen,&nbsp;Samuel Allemann,&nbsp;Cornelia Schneider","doi":"10.2147/PGPM.S382214","DOIUrl":"https://doi.org/10.2147/PGPM.S382214","url":null,"abstract":"<p><strong>Purpose: </strong>In Switzerland 167 drugs on the market contain information about pharmacogenetics in their drug label (PGx drug). Preemptive pharmacogenetic testing is reimbursed by health care insurance for only seven drugs (abacavir, carbamazepine, 6-mercaptopurine, azathioprine, 5-fluorouracil, capecitabine, and irinotecan) although, it is proposed to be a cost-effective approach to personalized medicine. The aim of this study was to describe the use of PGx drugs and their corresponding genes in Switzerland.</p><p><strong>Methods: </strong>We identified 90 drugs with dosing recommendations from the Pharmacogenetic Knowledgebase involving 24 genes. We assessed the utilization of those drugs between 2016 and 2020, using claims data from a large Swiss insurance company (Helsana).</p><p><strong>Results: </strong>Of 841 491 persons with drug claims during the whole study period, 78.7% were exposed to PGx drugs. Ibuprofen, pantoprazole, and tramadol had the highest number of users. Seven genes (<i>CYP2C19, CYP2C9, CYP2D6, SLCO1B1, HLA-B, MT-RNR1</i>, and <i>VKORC1</i>) were responsible for over 95% of all potential drug-gene interactions.</p><p><strong>Conclusion: </strong>The prevalence of PGx drug prescriptions is high in the Swiss population. Therefore, intensified preemptive testing may be a useful option as a substantial amount of the Swiss population might benefit.</p>","PeriodicalId":509088,"journal":{"name":"Pharmacogenomics and Personalized Medicine","volume":" ","pages":"967-976"},"PeriodicalIF":1.9,"publicationDate":"2022-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/39/dd/pgpm-15-967.PMC9701506.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40723062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CES1 and SLC6A2 Genetic Variants As Predictors of Response To Methylphenidate in Autism Spectrum Disorders.","authors":"Marta H Hernandez,&nbsp;Valentin Bote,&nbsp;Alexandre Serra-LLovich,&nbsp;Marc Cendros,&nbsp;Juliana Salazar,&nbsp;Conxita Mestres,&nbsp;Silvina Guijarro,&nbsp;Aida Alvarez,&nbsp;Cristina Lamborena,&nbsp;Iria Mendez,&nbsp;Bernardo Sanchez,&nbsp;Amaia Hervas,&nbsp;Maria J Arranz","doi":"10.2147/PGPM.S377210","DOIUrl":"https://doi.org/10.2147/PGPM.S377210","url":null,"abstract":"<p><strong>Purpose: </strong>Autistic spectrum disorders (ASD) children and adolescents usually present comorbidities, with 40-70% of them affected by attention deficit hyperactivity disorders (ADHD). The first option of pharmacological treatment for these patients is methylphenidate (MPH). ASD children present more side effects and poorer responses to MPH than ADHD children. The objective of our study is to identify genetic biomarkers of response to MPH in ASD children and adolescents to improve its efficacy and safety.</p><p><strong>Patients and methods: </strong>A retrospective study with a total of 140 ASD children and adolescents on MPH treatment was included. Fifteen polymorphisms within genes coding for the MPH target NET1 (<i>SLC6A2</i>) and for its primary metabolic pathway (<i>CES1</i>) were genotyped. Multivariate analyses including response phenotypes (efficacy, side-effects, presence of somnolence, irritability, mood alterations, aggressivity, shutdown, other side-effects) were performed for every polymorphism and haplotype.</p><p><strong>Results: </strong>Single marker analyses considering gender, age, and dose as covariates showed association between <i>CES1</i> variants and MPH-induced side effects (rs2244613-G (p=0.04), rs2302722-C (p=0.02), rs2307235-A (p=0.03), and rs8192950-T alleles (p=0.03)), and marginal association between the CES1 rs2302722-C allele and presence of somnolence (p=0.05) and the SLC6A2 rs36029-G allele and shutdown (p=0.05). A CES1 haplotype combination was associated with efficacy and side effects (p=0.02 and 0.03 respectively). SLC6A2 haplotype combination was associated with somnolence (p=0.05).</p><p><strong>Conclusion: </strong>CES1 genetic variants may influence the clinical outcome of MPH treatment in ASD comorbid with ADHD children and adolescents.</p>","PeriodicalId":509088,"journal":{"name":"Pharmacogenomics and Personalized Medicine","volume":" ","pages":"951-957"},"PeriodicalIF":1.9,"publicationDate":"2022-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/4e/47/pgpm-15-951.PMC9653043.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40694622","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Next-Generation Sequencing and Bioinformatics-Based Protocol for the Full-Length <i>CYP2E1</i> Gene Polymorphism Analysis.","authors":"Viktorija Igumnova,&nbsp;Agnija Kivrane,&nbsp;Anda Viksna,&nbsp;Inga Norvaisa,&nbsp;Renate Ranka","doi":"10.2147/PGPM.S371709","DOIUrl":"https://doi.org/10.2147/PGPM.S371709","url":null,"abstract":"<p><strong>Introduction: </strong>Pharmacogenetics studies provide clinically relevant information on the identified associations between genetic variants and individual variability in drug response, which, in turn, offers great promise for guiding personalized drug therapy and clinical trial design. However, there is a lack of information concerning the evidence-based clinical annotations of specific <i>CYP2E1</i> genetic variants.</p><p><strong>Aim: </strong>To design and evaluate the next-generation sequencing-based method for full-length <i>CYP2E1</i> gene polymorphism analysis.</p><p><strong>Materials and methods: </strong>Seven gene-specific oligonucleotide primer pairs targeting overlapping <i>CYP2E1</i> gene fragments spanning all nine gene exons with interleaving introns, untranslated (UTR) and intergenic regions were designed. Human DNA samples (n = 3) were used as a training set to check the primer performance and to optimize the PCR conditions. The effectiveness of the developed target amplification and sequencing protocol was evaluated using the test set comprising human DNA samples (n = 3) obtained from tuberculosis patients. Sequencing data analysis was performed on the Galaxy online-based platform.</p><p><strong>Results: </strong>The sequencing data quality was sufficient for the detection of genetic variants dispersed throughout the <i>CYP2E1</i> gene with a high degree of confidence in fully covered regions achieving optimal reading depth of the targeted fragment with high base call accuracy.</p><p><strong>Conclusion: </strong>Developed protocol can be applied in subpopulation-level association studies to determine whether single nucleotide variants (SNVs) or variant combinations from multiple regions of the <i>CYP2E1</i> gene are of clinical significance.</p>","PeriodicalId":509088,"journal":{"name":"Pharmacogenomics and Personalized Medicine","volume":" ","pages":"959-965"},"PeriodicalIF":1.9,"publicationDate":"2022-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/a3/be/pgpm-15-959.PMC9653044.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40710817","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Utilizing Pharmacogenomics Results to Determine Opioid Appropriateness and Improve Pain Management in a Patient with Osteoarthritis.","authors":"Katie Pizzolato,&nbsp;David Thacker,&nbsp;Nicole Marie Del Toro-Pagán,&nbsp;Nishita S Amin,&nbsp;Abeer Hanna,&nbsp;Jacques Turgeon,&nbsp;Veronique Michaud","doi":"10.2147/PGPM.S385272","DOIUrl":"https://doi.org/10.2147/PGPM.S385272","url":null,"abstract":"<p><p>The opioid epidemic in the United States has exposed the need for providers to limit opioid dispensing and identify at-risk patients prior to prescribing opioids. With pharmacogenomic testing, clinicians can analyze hundreds of medications-including commonly prescribed opioids-against genetic results to understand and predict risk and response. Moreover, knowledge of genotypic variants and altered function can help decrease trial and error prescribing, identify patients at-risk for adverse drug events, and improve pain control. This patient case demonstrates how pharmacogenomic test results identified drug-gene interactions and provided insight about a patient's inadequate opioid therapy response. With pharmacogenomic information, the patient's healthcare team discontinued opioid therapy and selected a more appropriate regimen for osteoarthritis (ie, celecoxib), resulting in improved pain control and quality of life.</p>","PeriodicalId":509088,"journal":{"name":"Pharmacogenomics and Personalized Medicine","volume":" ","pages":"943-950"},"PeriodicalIF":1.9,"publicationDate":"2022-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/e5/0e/pgpm-15-943.PMC9651068.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40710816","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role of Single Nucleotide Polymorphisms in Transporter Proteins and the Folate Metabolism Pathway in Delayed Methotrexate Excretion: A Case Report and Literature Review.","authors":"Jun Wang,&nbsp;Yue-Tao Zhao,&nbsp;Meng-Jiao Sun,&nbsp;Feng Chen,&nbsp;Hong-Li Guo","doi":"10.2147/PGPM.S376797","DOIUrl":"https://doi.org/10.2147/PGPM.S376797","url":null,"abstract":"<p><p>High-dose methotrexate (HDMTX) is a pivotal component of the chemotherapeutic regimens of osteosarcoma. However, the use of HDMTX is limited by an increased risk of dose-dependent toxicity. It is thought that the plasma levels and therapy-related toxicity of MTX could be associated with single nucleotide polymorphisms (SNPs) within MTX metabolism pathway genes. Here, we report a case of a paediatric osteosarcoma girl with delayed MTX excretion who was successfully managed using supportive measures and continuous veno-venous haemodiafiltration. We further identified the cause that could account for delayed elimination by genotyping analysis. The results showed that variations have been found in <i>SLCO1B1, SLC19A1, ABCB1</i> and <i>MTHFR</i>, all those were reported to have a strong association with delayed elimination of MTX in clinical studies. After comprehensive consideration of genotype and clinical phenotype, the second course of HDMTX was administered to this patient at a half reduced dose. We also performed a literature review to summarize the pharmacogenetic factors that influence HDMTX pharmacokinetics or MTX-related adverse effects in osteosarcoma patients. It is suggested that the potential risk of delayed MTX elimination is worthy of clinical attention, and the implementation of genotyping should be considered to ensure therapeutic safety.</p>","PeriodicalId":509088,"journal":{"name":"Pharmacogenomics and Personalized Medicine","volume":" ","pages":"919-926"},"PeriodicalIF":1.9,"publicationDate":"2022-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/f3/19/pgpm-15-919.PMC9637359.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40462077","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"What Personalized Medicine Humans Need and Way to It --also on the Practical Significance and Scientific Limitations of Precision Medicine.","authors":"Bing Yuan","doi":"10.2147/PGPM.S380767","DOIUrl":"https://doi.org/10.2147/PGPM.S380767","url":null,"abstract":"<p><p>The rise of precision medicine has opened up a broad space for the development of modern medicine and has also given practical significance to the concept of personalised medicine. Precision medicine is establishing a personalized disease classification system that differs from the traditional system. However, the research progress of precision medicine in recent years is far from satisfactory: There are few disease types that can be attributed to the abnormality of a single target; the effects of current'precision' medications are not ideal, and various side effects remain unavoidable. The methodology of precision medicine is still reductionist, and it would not solve the integration problem of clinical treatment but rather would increase the difficulty of integration. Therefore, the precision medicine approach is not a feasible way to build a personalised medicine system. Based on the analysis and demonstration of the scientific limitations of precision medicine and the consistency of traditional Chinese medicine (TCM) and complexity science methods, this paper draws on the concepts and methods of cybernetics and complexity science, and proposes a fresh set of ideas and methods for the development of personalised medicine. The conclusion is as follows: Along the path of precision medicine, ideal personalised medicine cannot be achieved; what people ultimately need is personalised medicine that can achieve holistic integration. On the basis of TCM with the characteristics of holistic integration and personalisation, and according to scientific norms and the principle of evidence, building a theoretical model and state description system grounded in empirical evidence is the best way to establish a personalised medicine system.</p>","PeriodicalId":509088,"journal":{"name":"Pharmacogenomics and Personalized Medicine","volume":" ","pages":"927-942"},"PeriodicalIF":1.9,"publicationDate":"2022-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/0c/ae/pgpm-15-927.PMC9640219.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40675404","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mowat-Wilson Syndrome as a Differential Diagnosis in Patients with Congenital Heart Defects and Dysmorphic Facies.","authors":"Harry Pachajoa,&nbsp;Eidith Gomez-Pineda,&nbsp;Sebastian Giraldo-Ocampo,&nbsp;Juliana Lores","doi":"10.2147/PGPM.S380908","DOIUrl":"https://doi.org/10.2147/PGPM.S380908","url":null,"abstract":"<p><p>Mowat-Wilson syndrome is a rare, autosomal dominant neurodevelopmental disorder characterized by distinctive facial gestalt and intellectual disability that is often associated with microcephaly, seizures and multiple congenital anomalies, mainly heart defects. More than 350 patients and 180 genetic variants in the <i>ZEB2</i> gene, have been reported with an estimated frequency of 1 per 70,000 births. Here we report a Colombian female patient with facial gestalt, intellectual disability, microcephaly, congenital heart defects, hypothyroidism and middle ear defect associated with the nonsense pathogenic variant c.2761C>T (p.Arg921Ter) in the <i>ZEB2</i> gene. This case contributes to the understanding of the clinical complications and the natural history of this complex and clinically heterogeneous disorder but also to the awareness that patients with heart congenital defects and dysmorphic facies may present an underlying genetic disorder.</p>","PeriodicalId":509088,"journal":{"name":"Pharmacogenomics and Personalized Medicine","volume":" ","pages":"913-918"},"PeriodicalIF":1.9,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/a6/51/pgpm-15-913.PMC9636884.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40672099","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}