Pharmacogenomics and Personalized Medicine最新文献

{"title":"Association of Genetic Variants in miR-217 Gene with Risk of Coronary Artery Disease: A Case-Control Study.","authors":"Xia Han,&nbsp;Xiaotang Liang,&nbsp;Menghai Wu,&nbsp;Lijun Zhang,&nbsp;Honglei Jiang","doi":"10.2147/PGPM.S324767","DOIUrl":"https://doi.org/10.2147/PGPM.S324767","url":null,"abstract":"<p><strong>Objective: </strong>To evaluate the associations of genetic variants of the miR-217 gene with coronary artery disease (CAD) risk, as well as plasma level of vascular endothelial growth factor (VEGF).</p><p><strong>Methods: </strong>A case-control study with 498 CAD patients and 499 frequency-matched healthy controls was conducted to evaluate the associations of four tagSNPs of the miR-217 gene, including rs6724872, rs4999828, rs10206823, and rs41291177, with CAD risk and plasma level of VEGF.</p><p><strong>Results: </strong>SNP rs6724872 and rs4999828 were significantly associated with increased risk of CAD (P value was smaller than 0.05 even after Bonferroni multiple adjustment). Compared with the G allele, C allele of rs6724872 was significantly associated with 1.73-fold increased risk of CAD (95% CI: 1.25-2.39; P = 0.001). While C allele of rs4999828 was significantly associated with 1.75-fold increased risk of CAD, compared with T allele (95% CI: 1.34-2.29; P = 4 × 10^-5). Meanwhile, rs6724872 and rs4999828 were also significantly associated with higher level of VEGF (P < 0.001).</p><p><strong>Conclusion: </strong>These findings highlighted the important role of genetic variants of the miR-217 gene in the pathogenesis of CAD and potential targets for intervention.</p>","PeriodicalId":509088,"journal":{"name":"Pharmacogenomics and Personalized Medicine","volume":" ","pages":"1081-1086"},"PeriodicalIF":1.9,"publicationDate":"2021-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/12/b7/pgpm-14-1081.PMC8409599.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39385396","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":"Genetic and Non-Genetic Factors Impact on INR Normalization in Preprocedural Warfarin Management.","authors":"Islam Eljilany,&nbsp;Mohamed Elarref,&nbsp;Nabil Shallik,&nbsp;Abdel-Naser Elzouki,&nbsp;Loulia Bader,&nbsp;Ahmed El-Bardissy,&nbsp;Osama Abdelsamad,&nbsp;Daoud Al-Badriyeh,&nbsp;Larisa H Cavallari,&nbsp;Hazem Elewa","doi":"10.2147/PGPM.S322743","DOIUrl":"https://doi.org/10.2147/PGPM.S322743","url":null,"abstract":"<p><strong>Background: </strong>Annually, 10% of warfarin patients will likely need to stop warfarin prior to elective surgery to achieve a baseline international normalization ratio (INR) level (INR ≤ 1.2) at the time of the procedure. This study explores the influence of genetic and non-genetic factors on INR normalization in the Arab (major part of Near Eastern) population in preprocedural warfarin management.</p><p><strong>Methods: </strong>An observational prospective cohort study was designed to recruit Arab patients taking warfarin and scheduled for an elective procedure. Two INR readings were recorded. DNA extraction and genotyping of variants in <i>CYP2C9*2, CYP2C9*3, CYP4F2*3, VKORC1*2</i>, and <i>FII</i> (rs5896) and <i>FVII</i> (rs3093229) genes using real-time polymerase chain reaction were performed.</p><p><strong>Results: </strong>Data from 116 patients were included in the analysis. <i>CYP2C9</i> and <i>VKORC1</i> genetic variants carriers required lower maintenance dose compared to non-carriers. The analysis showed that ciprofloxacin, antiplatelet medications, and INR index (INR at visit 1) are the only factors associated with the INR decline rate. Also, the proportion of <i>CYP2C9*3</i> carriers with normal INR (≤1.2) on the day of surgery was significantly lower than those with wild-type genotype (28% vs 60%, <i>p</i>=0.013). In addition, heparin bridging, INR target, and Sudanese nationality are significant predictors of INR normalization (≤1.2) on the day of the procedure.</p><p><strong>Conclusion: </strong>Despite the confirmed effect of genetic factors on warfarin maintenance dose, the study was not able to find a significant effect of any genetic factor on the rate of INR normalization possibly due to the small sample size. Index INR and interacting medications showed to be significant predictors of INR decline rate.</p>","PeriodicalId":509088,"journal":{"name":"Pharmacogenomics and Personalized Medicine","volume":" ","pages":"1069-1080"},"PeriodicalIF":1.9,"publicationDate":"2021-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/e8/8c/pgpm-14-1069.PMC8409603.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39385450","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":"Genetic Polymorphisms of <i>FCRL3, NLRP3</i> and <i>IL2</i> are Associated with the Risk of Head and Neck Cancer in a Chinese Population.","authors":"Yuhao Zhang,&nbsp;Dawei Sun","doi":"10.2147/PGPM.S324750","DOIUrl":"https://doi.org/10.2147/PGPM.S324750","url":null,"abstract":"<p><strong>Purpose: </strong>This study aimed to evaluate the associations between immune-related gene (<i>FCRL3, NLRP3</i> and <i>IL2</i>) polymorphisms and the risk of head and neck cancer (HNC).</p><p><strong>Methods: </strong>Six polymorphisms of <i>FCRL3, NLRP3</i> and <i>IL2</i> were genotyped in 400 HNC cases and 400 controls using a MassARRAY platform.</p><p><strong>Results: </strong>rs11264799-T was a protective variant against HNC risk, while rs7528684-G, rs35829419-A and rs6822844-T were all risk alleles for HNC (<i>p</i> < 0.05). rs11264799-TT was correlated with reduced HNC risk, while rs7528684-GG and rs6822844-TG were associated with an elevated risk of disease (<i>p</i> < 0.05). Moreover, rs11264799 was correlated with a declining risk of HNC in three genetic models (<i>p</i> < 0.05). In contrast, rs7528684 exhibited an elevated risk of HNC in recessive and additive models; rs35829419 and rs6822844 were associated with an increased risk of disease in dominant and additive models (<i>p</i> < 0.05). Finally, an interaction was observed between the above SNPs and drinking (<i>p</i> < 0.05).</p><p><strong>Conclusion: </strong>The results expand our knowledge on immune-related gene polymorphisms in HNC and provide clues for further functional study on the pathogenesis of HNC.</p>","PeriodicalId":509088,"journal":{"name":"Pharmacogenomics and Personalized Medicine","volume":" ","pages":"1047-1053"},"PeriodicalIF":1.9,"publicationDate":"2021-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/28/96/pgpm-14-1047.PMC8405226.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39392295","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":"A Chinese Boy with Mowat-Wilson Syndrome Caused by a 10 bp Deletion in the <i>ZEB2</i> Gene.","authors":"Lin Wei,&nbsp;Xiao Han,&nbsp;Xue Li,&nbsp;Bingjuan Han,&nbsp;Wenying Nie","doi":"10.2147/PGPM.S320128","DOIUrl":"https://doi.org/10.2147/PGPM.S320128","url":null,"abstract":"<p><strong>Purpose: </strong>Mowat-Wilson syndrome (MWS) is a rare complex malformation syndrome which is characterized by typical facial dysmorphism, moderate to severe intellectual disability, global developmental delay, and multiple congenital anomalies. Here, we summarize the clinical characteristics and gene mutation analysis of a Chinese boy with MWS.</p><p><strong>Patients and methods: </strong>The clinical features of the patient were monitored. DNA extracted from peripheral blood was subjected to sequencing analysis. Then, the whole-exome sequencing was performed.</p><p><strong>Results: </strong>A novel deletion mutation (c.1137_1146del TAGTATGTCT) was identified in exon 8 of the <i>ZEB2</i> gene. The deletion mutation was predicted to produce a truncated protein (p.S380Nfs*13), resulting in haploinsufficiency. The patient presented with short stature, microcephaly, congenital heart defects, cryptorchidism, corpus callosum agenesis, global developmental delay, and intellectual disability. Furthermore, he demonstrated bilateral sensorineural hearing loss. This manifestation is less common in MWS. It is first reported in Chinese patients with MWS. Clinical follow-up showed that the facial features of MWS developed with time. The facial features of the patient were not obvious except for the uplifted ear lobes at the age of 3 months. At the age of 22 months, the facial characteristics of the patient included ocular hypertelorism, frontal bossing, rounded nasal tip, sparse eyebrows, prominent chin, widely spaced teeth, and uplifted ear lobes with a central depression.</p><p><strong>Conclusion: </strong>A novel deletion mutation of the <i>ZEB2</i> gene was identified. This work contributes to expanding the mutation spectra of MWS. Our results may reflect the variability of the phenotype in MWS.</p>","PeriodicalId":509088,"journal":{"name":"Pharmacogenomics and Personalized Medicine","volume":" ","pages":"1041-1045"},"PeriodicalIF":1.9,"publicationDate":"2021-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/9c/10/pgpm-14-1041.PMC8396371.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39371380","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":"Long Non-Coding RNAs Gene Variants as Molecular Markers for Diabetic Retinopathy Risk and Response to Anti-VEGF Therapy.","authors":"Hala M F Mohammad,&nbsp;Ahmed A Abdelghany,&nbsp;Essam Al Ageeli,&nbsp;Shahad W Kattan,&nbsp;Ranya Hassan,&nbsp;Eman A Toraih,&nbsp;Manal S Fawzy,&nbsp;Naglaa Mokhtar","doi":"10.2147/PGPM.S322463","DOIUrl":"https://doi.org/10.2147/PGPM.S322463","url":null,"abstract":"<p><strong>Background: </strong>Long non-coding RNAs (lncRNAs) play essential roles in molecular diagnosis and therapeutic response in several diseases.</p><p><strong>Purpose: </strong>For the first time, we aimed to evaluate the association of four lncRNAs <i>TUG1</i> (<i>rs7284767G/A), MIAT</i> (rs1061540T/C), <i>MALAT1</i> (rs3200401C/T), and <i>SENCR</i> (rs12420823C/T) variants with susceptibility to diabetic retinopathy (DR), disease severity, and early therapeutic response to intravitreous anti-vascular endothelial growth factor aflibercept therapy.</p><p><strong>Patients and methods: </strong>This case-control study enrolled 126 adult patients with type 2 diabetes. TaqMan assays using Real-Time PCR were run for genotyping. Multivariable regression analyses were applied to assess the role of each polymorphism after the adjustment of covariates.</p><p><strong>Results: </strong>Carriers of <i>TUG1</i> A/G and <i>MIAT</i> T/C and C/C genotypes were more likely to develop DR [OR=3.15 (95% CI=1.15-8.64), and OR=4.31 (95% CI=1.78-10.47)], while <i>MALAT1</i> T/C conferred protection (OR=0.40, 95% CI=0.16-0.99). For <i>TUG1, MALAT1, MIAT</i>, and <i>SENCR</i> genotype combinations, GTCT and GCCC had a higher disease risk (<i>P</i>=0.012). For disease severity, <i>MIAT</i> T/T homozygosity was associated with higher DR grade [33.3% (T/T) vs 10% (C/C) and 4.2% (C/T) carriers, <i>P</i>=0.012]. Otherwise, patients with the <i>SENCR</i> T variant exhibited better pre-treatment best-corrected visual acuity level (<i>p</i>=0.021). Following aflibercept administration, carrying the <i>TUG1</i> A or <i>MIAT</i> T/C was associated with a poor therapeutic response (OR=5.02, 95% CI=1.60-15.76, and OR=10.23, 95% CI=1.51-69.15, respectively).</p><p><strong>Conclusion: </strong>The lncRNAs <i>TUG1</i> (<i>rs7284767G/A)</i> and <i>MIAT</i> (rs1061540T/C) were associated with increased DR susceptibility and poor response to aflibercept treatment, while <i>MALAT1</i> (rs3200401C/T) conferred protection to DR. These genetic determinants could be useful in DR risk stratification and pharmacogenetics after validation in large-scale studies.</p>","PeriodicalId":509088,"journal":{"name":"Pharmacogenomics and Personalized Medicine","volume":" ","pages":"997-1014"},"PeriodicalIF":1.9,"publicationDate":"2021-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/a2/05/pgpm-14-997.PMC8374537.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39343066","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 Value of Population Screening in Advancing Personalized Medicine in the Field of Lung Cancer.","authors":"Alice Mogenet,&nbsp;Laurent Greillier,&nbsp;Pascale Tomasini","doi":"10.2147/PGPM.S267437","DOIUrl":"https://doi.org/10.2147/PGPM.S267437","url":null,"abstract":"<p><p>During the past decade, progress has been made in the field of lung cancer molecular biology and onco-immunology, leading to prolonged survival of patients. The combination of increased fundamental knowledge and the pharmaceutical pipeline has allowed the development of various tyrosine kinase inhibitors, targeting numerous molecular alterations. These drugs are now available in daily practice and have transformed survival outcomes for patients harboring <i>EGFR, ALK</i> or <i>ROS1</i> alterations. Multiple clinical trials are now ongoing in order to increase the number of approved drugs, thus overcoming the issues of rare mutations and tyrosine kinase inhibitors resistance. Immune checkpoint inhibitors development has also changed lung cancer outcomes, but underwhelming response rates highlight the need for immune biomarkers. While PD-L1 expression was the first approved immune biomarker, it has shown several limitations and new biomarkers have to be identified to predict response or resistance to immune checkpoint inhibitors. Testing methods, molecular results and targeted therapeutic schedules will be harmonized in the coming years, with the help of dedicated molecular multidisciplinary boards.</p>","PeriodicalId":509088,"journal":{"name":"Pharmacogenomics and Personalized Medicine","volume":" ","pages":"987-996"},"PeriodicalIF":1.9,"publicationDate":"2021-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/36/fe/pgpm-14-987.PMC8374839.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39340616","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":"Association Between Insomnia and Migraine Risk: A Case-Control and Bidirectional Mendelian Randomization Study.","authors":"Shujuan Chu,&nbsp;Zhilin Wu,&nbsp;Zhouyang Wu,&nbsp;Jing Wu,&nbsp;Yue Qian","doi":"10.2147/PGPM.S305780","DOIUrl":"https://doi.org/10.2147/PGPM.S305780","url":null,"abstract":"<p><strong>Background: </strong>The causal relationship between insomnia and migraine is contradictory and no study has been carried out among the Chinese population to date.</p><p><strong>Methods: </strong>In this case, we conducted a case-control study and a bidirectional mendelian randomization (MR) analysis to determine whether insomnia is causally related to the development of migraine. The instrumental variables for insomnia were derived from the largest genome-wide association study of 1,331,010 participants, while the genetic instruments for migraine were available from the largest meta-analysis of migraine with 59,674 cases and 316,078 controls.</p><p><strong>Results: </strong>In case-control study, subjects with insomnia have significantly higher risk of migraine (OR=4.29, 95% CI: 3.21-5.74, P<0.001), compared with those without insomnia. The bidirectional two-sample MR analysis revealed that insomnia was significantly associated with higher risk of migraine (OR=1.24, 95% CI: 1.11-1.38, P=1.01×10-4), and the results were validated in the UK Biobank data. The results showed no indication for directional pleiotropy effects as assessed by the MR-Egger intercept (P>0.05).</p><p><strong>Conclusion: </strong>Conclusively, our study highlighted that increased migraine risk was confined to subjects with a genetic pre-disposition to insomnia, and these findings had potential implications for improving the sleep quality to reduce the burden of migraine.</p>","PeriodicalId":509088,"journal":{"name":"Pharmacogenomics and Personalized Medicine","volume":" ","pages":"971-976"},"PeriodicalIF":1.9,"publicationDate":"2021-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/b2/53/pgpm-14-971.PMC8370591.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39329072","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":"Genetic Variation of Inflammatory Genes to Ischemic Stroke Risk in a Chinese Han Population.","authors":"Zhongqiu Zhang,&nbsp;Yanping Mei,&nbsp;Mengqiu Xiong,&nbsp;Fang Lu,&nbsp;Xianghong Zhao,&nbsp;Junrong Zhu,&nbsp;Bangshun He","doi":"10.2147/PGPM.S320483","DOIUrl":"https://doi.org/10.2147/PGPM.S320483","url":null,"abstract":"<p><strong>Background: </strong>Inflammation proteins play an important role in stroke occurrence. <i>IL1A, IL1B, PTGS2, MMP2</i>, and <i>MMP9</i> were the mediators involved in the immune response, and the association of these genetic variations with ischemic stroke (IS) risk was still unclear.</p><p><strong>Methods: </strong>To investigate the susceptibility of genetic variations of <i>IL1A, IL1B, PTGS2, MMP2</i>, and <i>MMP9</i> to IS risk, we performed a case-control study involving 299 patients and 300 controls in a Chinese population. Thirteen genetic variations of investigated genes of all participants were genotyped using an improved multiplex ligase detection-reaction technique.</p><p><strong>Results: </strong>No SNP in all genes showed an association with overall IS. However, in subgroup analysis, <i>PTGS2</i> rs689466 (dominant model: CT vs TT - OR_adjusted= 2.51, 95% CI: 1.22-5.16, <i>p</i> = 0.012; co-dominant model: CT/CC vs TT - OR_adjusted= 2.53, 95% CI: 1.26-5.07, p = 0.009; additive model - OR_adjusted= 2.26, 95% CI: 1.19-4.28, <i>p</i> = 0.013) and rs5275 (dominant model: GG vs AA - OR_adjusted= 0.31, 95% CI: 0.12-0.80, <i>p</i> = 0.016; co-dominant model: GA/GG vs AA - OR_adjusted= 0.45, 95% CI: 0.21-0.95, <i>p</i> = 0.036; additive model - OR_adjusted= 0.60, 95% CI: 0.39-0.92, <i>p</i> = 0.020) were associated with IS type of small-vessel occlusion.</p><p><strong>Conclusion: </strong>Our study suggested that <i>PTGS2</i> rs689466 C and rs5275 A were potentially associated with IS subtype of small-vessel occlusion. Our result should be confirmed with further large sample sized studies.</p>","PeriodicalId":509088,"journal":{"name":"Pharmacogenomics and Personalized Medicine","volume":" ","pages":"977-986"},"PeriodicalIF":1.9,"publicationDate":"2021-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/69/fe/pgpm-14-977.PMC8370589.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39329073","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":"Case Report: Fatigue and Bleeding in a Polymedicated Patient Using Several Herbal Supplementations, Detected with g-Nomic^® Software.","authors":"Abel Saldarreaga Marin,&nbsp;Marc Cendros,&nbsp;Carlos J Ciudad,&nbsp;Ana Sabater","doi":"10.2147/PGPM.S323463","DOIUrl":"https://doi.org/10.2147/PGPM.S323463","url":null,"abstract":"<p><p>This was a case report of severe fatigue and bleeding in a 65-year-old man with ischemic heart disease who was wearing a stent and taking multiple medications for hypertension and diabetes. The use of a drug interaction and personalized prescription software (g-Nomic^®) revealed potential interactions, involving acetylsalicylic acid and several non-pharmaceutical products including ginger, blueberry extracts, pineapple juice, docosahexaenoic acid and liquorice. Correction of these interactions resulted in complete remission of the reported side effects. This supports the idea that non-pharmaceuticals potentiated the effects of acetylsalicylic acid on haemostasis, producing the bleeding that would have caused fatigue. It is important to use appropriate tools to detect drug interactions that also take into account commonly used non-pharmaceutical products. Drug interactions can be considered illnesses by themselves.</p>","PeriodicalId":509088,"journal":{"name":"Pharmacogenomics and Personalized Medicine","volume":" ","pages":"963-970"},"PeriodicalIF":1.9,"publicationDate":"2021-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/73/4b/pgpm-14-963.PMC8367204.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39324162","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":"Individualized Drugs' Selection by Evaluation of Drug Properties, Pharmacogenomics and Clinical Parameters: Performance of a Bioinformatic Tool Compared to a Clinically Established Counselling Process.","authors":"Marina Borro,&nbsp;Giovanna Gentile,&nbsp;Sally H Preissner,&nbsp;Leda Marina Pomes,&nbsp;Björn-Oliver Gohlke,&nbsp;Antonio Del Casale,&nbsp;Andreas Eckert,&nbsp;Paolo Marchetti,&nbsp;Saskia Preissner,&nbsp;Robert Preissner,&nbsp;Maurizio Simmaco","doi":"10.2147/PGPM.S316556","DOIUrl":"https://doi.org/10.2147/PGPM.S316556","url":null,"abstract":"<p><strong>Purpose: </strong>Inefficacy and safety concerns are main medications' problems, especially in the case of poly-therapies, when drug-drug interactions may alter the expected drug disposition. Ongoing efforts are aimed to establish drug selection processes aimed to preemptive evaluation of a plethora of factors affecting patient's specific drug response, including pharmacogenomic markers, in order to minimize prescription of improper medications. In previous years, we established at the University Hospital Sant'Andrea of Rome, Italy, a Precision Medicine Service based on a multi-disciplinary experts' team. The team is in charge to produce a drug therapy counselling report, including pharmacogenomic, pharmacokinetic and pharmacodynamic considerations. In this study, we aimed to evaluate the performance of this established \"manual\" process of therapy selection with a novel bioinformatic tool, the Drug-PIN system.</p><p><strong>Patients and methods: </strong>A total of 200 patients diagnosed with Major Depressive Disorders or a depressive episode in Bipolar Disorder, with at least three previous failed treatments, who underwent pharmacogenomic profiling and therapy counselling in the Sant'Andrea Hospital from 2017 to 2020. The baseline poly-therapy of these patients was re-evaluated and optimized by Drug-PIN. Results of the Drug-PIN poly-therapy evaluation/optimization were compared with the results of the original poly-therapy evaluation/optimization by therapy counselling. To compare the results between the two processes, the risk associated with each poly-therapy was classified as low, moderate, or high.</p><p><strong>Results: </strong>The number of baseline poly-therapies classified in low-, moderate- or high-risk did not change significantly between manual system or Drug-PIN system. As the counselling process, also the Drug-PIN system produces a significant decrease in the predicted treatment-associated risk.</p><p><strong>Conclusion: </strong>Drug-PIN substantially replicates the output of the counselling process, allowing a substantial reduction in the time needed for therapy evaluation. Availability of an effective bioinformatic tool for proper drug selection is expected to exponentially increase the actuation of targeted therapy strategies.</p>","PeriodicalId":509088,"journal":{"name":"Pharmacogenomics and Personalized Medicine","volume":" ","pages":"955-962"},"PeriodicalIF":1.9,"publicationDate":"2021-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/df/c1/pgpm-14-955.PMC8352633.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39307999","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}