Current Pharmacogenomics and Personalized Medicine最新文献

{"title":"Expression of Angiogenesis-related Genes in a Group of Iranian Cases of Breast Cancer","authors":"Seyyed Amir Yasin Ahmadi, S. Sayad, F. Shahsavar, Reza Nekouian, M. Panahi, Saed Sayad, M. B. Boroujeni, S. Akbari","doi":"10.2174/1875692117999201215161142","DOIUrl":"https://doi.org/10.2174/1875692117999201215161142","url":null,"abstract":"\u0000\u0000This study aims to design an angiogenesis gene expression profile; to study angiogenesis gene\u0000expression profile in breast cancer; and to map angiogenesis gene expression profile in individual participants.\u0000\u0000\u0000\u0000 In molecular etiology of each disease, there are some important molecules involved in the\u0000related pathways. From the viewpoint of precision medicine, molecular etiology of a disease is different\u0000person by person because of genetic variations of the genes involved in these pathways. This point of view\u0000intends researchers of drug development to design novel drugs for targeted therapy based on the exact etiology.\u0000In the case of angiogenesis, there is a drug profile parallel to the molecular profile. Bevacizumab,\u0000sunitinib and aflibercept are examples of anti-angiogenic drugs.\u0000\u0000\u0000\u0000 A hallmark of solid tumors is sustained angiogenesis. Vascular endothelial growth factors\u0000(VEGF), VEGF receptors (VEGFR) and placental growth factor (PlGF) are involved in angiogenesis. We\u0000aimed to study the gene expression profile of angiogenesis including VEGF-A, VEGF-B, VEGF-C,\u0000VEGF-D, VEGFR-1, VEGFR-2, VEGFR-3 and PlGF in an Iranian group of patients undergoing breast\u0000surgery due to breast cancer and breast fibroadenoma.\u0000\u0000\u0000\u0000Tumor tissue samples of a group of patients with invasive ductal carcinoma (IDC) and a group\u0000of patients with fibroadenoma (Fib) were used. Gene expression was studied by real-time quantitative\u0000polymerase chain reaction (q-PCR) and fold changes (FC) with their 95% confidence intervals (CI) were\u0000reported based on calibration with normal breast tissue.\u0000\u0000\u0000\u0000All the genes showed significant up-regulation in IDC group. The extensive up-regulation was\u0000for VEGFR-2 (FC=52.68; 95% CI=17.96-154.47; P<0.001). In Fib group, PlGF showed a significant upregulation\u0000(FC=10.41; 95% CI=5.35-20.26; P=0.002). Comparison of IDC group with Fib group showed\u0000significant up-regulation of VEGFR-1, VEGFR-2 and VEGFR-3 in IDC group (P<0.05).\u0000\u0000\u0000\u0000 Malignancy of breast tumors is associated with overexpression of all the genes of this profile.\u0000However, only VEGFRs showed up-regulation in comparison to benign tumors. Individualized targeted\u0000therapy, according to this profile, should be studied in the future.\u0000","PeriodicalId":11056,"journal":{"name":"Current Pharmacogenomics and Personalized Medicine","volume":"26 1","pages":"197-205"},"PeriodicalIF":0.0,"publicationDate":"2021-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75049474","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":"AtreMorine Treatment Regulates DNA Methylation in Neurodegenerative Disorders: Epigenetic and Pharmacogenetic Studies","authors":"Olaia A. Martínez-Iglesias, V. Naidoo, J. Carril, Iván Carrera, L. Corzo, Susana Rodríguez, Ramón Alejo, Natalia Cacabelos, R. Cacabelos","doi":"10.2174/1875692117999201231152800","DOIUrl":"https://doi.org/10.2174/1875692117999201231152800","url":null,"abstract":"\u0000\u0000Neurodegenerative disorders are one of the major health problems\u0000in Western countries. Genetic and epigenetic mechanisms play crucial roles in the\u0000origin and progression of these disorders. DNA methylation is the most widely studied epigenetic\u0000mark and is an important regulator of gene expression.\u0000\u0000\u0000\u0000Little is known about the influence of bioactive dietary components on epigenetic\u0000mechanisms in neurodegenerative diseases. In this study, we investigated the effects\u0000of E-PodoFavalin-15999 (AtreMorine®), a bioproduct with potent neuroprotective and dopamine\u0000enhancing capabilities, on DNA methylation patterns in Alzheimer’s (AD) and\u0000Parkinson’s Disease (PD). We also aimed to assess, in patients with PD, the effects that\u0000genetic variation across candidate pharmacogenes may have on dopamine synthesis and\u0000release in response to treatment with AtreMorine.\u0000\u0000\u0000\u0000We analyzed global DNA methylation and de novo DNA methyltransferase\u0000(DNMT) expression in a transgenic (3xTg) mouse model of AD, and further examined\u0000global DNA methylation in blood samples from patients with PD.\u0000\u0000\u0000\u0000AtreMorine treatment increased global DNA methylation in 3xTg mice and in\u0000patients with Parkinson´s disease, and produced high DNMT3a expression in AD mice.\u0000We observed varied responses to AtreMorine across the following pharmacogenetic genophenotypes\u0000analyzed, cytochrome P450 oxidases (CYP2D6, CYP2C19, CYP2C9,\u0000CYP3A4, CYP3A5, CYP1A2), human arylamine N-acetyltransferase 2 (NAT2), the vitamin\u0000K epoxide reductase complex subunit 1 (VKORC1), ATP-binding cassette subfamily B\u0000member 1 (ABCB1), and solute carrier organic anion transporter family member 1B1\u0000(SLCOB1).\u0000\u0000\u0000\u0000 Our results suggest that AtreMorine regulates DNA methylation in neurodegenerative\u0000disorders and may constitute a new therapeutic option for the treatment of\u0000these pathologies.\u0000","PeriodicalId":11056,"journal":{"name":"Current Pharmacogenomics and Personalized Medicine","volume":"1 1","pages":"159-171"},"PeriodicalIF":0.0,"publicationDate":"2021-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77647384","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":"Gene Frequency of CYP2D6*4 and *10 Variants in Karachi Population","authors":"T. Fatima, Farah Zeb, A. Farooq","doi":"10.2174/1875692117999201014162804","DOIUrl":"https://doi.org/10.2174/1875692117999201014162804","url":null,"abstract":"\u0000\u0000 In the human population, CYP2D6 is highly polymorphic group of\u0000genes involved in metabolizing ~25% of all clinically used neuroleptic and antidepressant\u0000drugs. The CYP2D6*4 and CYP2D6*10 variants are prevalent in Asian population exhibiting\u0000variable drug metabolizing ability thereby affecting drug therapeutic responses.\u0000\u0000\u0000\u0000To determine the genotypic frequencies of CYP2D6*1 (Normal metabolizer), *4\u0000(Poor metabolizer) and *10 (Intermediate metabolizer) variants among schizophrenic subjects\u0000and control group from a sub-set of Karachi population.\u0000\u0000\u0000\u0000Genomic Deoxyribonucleic Acid (gDNA) was extracted and amplified with\u0000CYP2D6*4 and *10 primers using Polymerase Chain Reaction (PCR) and digested by Bacillus\u0000stereothermophilus (BstN1) and Hemophilus parahemolyticus (Hph1) restriction enzymes. The\u0000digested gDNA bands were identified as wild type or mutants and their genotypic frequencies\u0000were estimated by Hardy-Weinberg Equation (HWE).\u0000\u0000\u0000\u0000 In normal subjects, frequencies of CYP2D6*1 wild allele (57%) coded functional enzyme,\u0000CYP2D6*4 variant (9%) producing non-functional enzyme and CYP2D6*10 allele (70%)\u0000producing altered enzyme with reduced activity that was most prevalent in schizophrenic patients.\u0000\u0000\u0000\u0000Drug response is a complex phenomenon that is governed by genetic and environmental\u0000factors. Antipsychotic drug metabolism among schizophrenic patients with variable drug\u0000responsesis related to CYP2D6 polymorphism. Clinically, it is imperative to differentiate between\u0000responders and non-responders using the treatment, otherwise the drug will be either nonefficacious\u0000or toxic to the patients. Therefore, a gene testing system needs to be established to\u0000identify patient’s genotype(s) predicting whether they are normal, poor, intermediate or ultrarapid\u0000drug metabolizer thereby allowing clinicians to adjust dose(s) of antipsychotic drug(s).\u0000\u0000\u0000\u0000Genotyping of CYP2D6 alleles among schizophrenic patients indicated prevalence\u0000of *4 and *10 variants in Karachi population producing non-functional (poor metabolizer)\u0000and reduced functional (intermediate metabolizer) drug metabolizing enzymes phenotypes,\u0000respectively. Hence, dose adjustment is crucial otherwise schizophrenia condition will not be\u0000improved satisfactorily. Therefore, CYP2D6 gene screening program should be included in\u0000clinical practice to help clinicians to prescribe appropriate doses according to patient’s genotype\u0000and minimize sufferings of schizophrenics including side effects of drug that might occur\u0000at high drug concentrations.\u0000","PeriodicalId":11056,"journal":{"name":"Current Pharmacogenomics and Personalized Medicine","volume":"3 7 1","pages":"172-181"},"PeriodicalIF":0.0,"publicationDate":"2021-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77816701","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":"Autosomal Recessive Hereditary Spastic Paraplegia: A Rare Case of a Family with Phenotypic Variation","authors":"M. Saban, Tal Shachar","doi":"10.2174/1875692117999201211142908","DOIUrl":"https://doi.org/10.2174/1875692117999201211142908","url":null,"abstract":"\u0000\u0000 Hereditary spastic paraplegia is a neurodegenerative disorder\u0000with a pure and complex form. More than 50 genetic types are currently known, with different\u0000ages of onset for characteristic symptoms. Data regarding hereditary spastic paraplegia\u0000remain scarce, and the rare subtype of spastic paraplegia type 5 is no exception.\u0000\u0000\u0000\u0000 This report presents data regarding the case of a single family, from the city of\u0000Djerba, with five individuals affected with hereditary spastic paraplegia, the largest number\u0000of spastic paraplegia type 5 mutated family members so far reported in current literature.\u0000\u0000\u0000\u0000To emphasize the importance of genetic testing, we retrospectively reviewed a\u0000familial confirmed case of hereditary spastic paraplegia. Clinical features of family members\u0000were described.\u0000\u0000\u0000\u0000The family presents a large phenotypic variation that, in part, differs from the\u0000known phenotypic presentations. Age of onset and clinical manifestation showed interfamilial\u0000variations. The alteration found in CYP7B1 (c.1081C>T; p.R361*) may help emphasize\u0000the importance of genetic testing and the much-needed treatment options already\u0000in use in current neurological practice.\u0000\u0000\u0000\u0000 The understanding of the molecular pathways of hereditary spastic paraplegia,\u0000together with the establishment of disease biomarkers, will hopefully lead to better\u0000and more personalized treatment.\u0000","PeriodicalId":11056,"journal":{"name":"Current Pharmacogenomics and Personalized Medicine","volume":"62 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90374623","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":"T Allele of the DRD2 Taq1 A Gene Polymorphism Increases the Predisposition to Drug Addiction in Indonesian Population","authors":"Viren Ramadhan, F. Rahman, A. Sadewa, Z. Ikawati","doi":"10.2174/1875692117999201211142201","DOIUrl":"https://doi.org/10.2174/1875692117999201211142201","url":null,"abstract":"\u0000\u0000 Dopamine plays an important role in mediating the rewarding\u0000properties in the abuse of drugs. The Taq1A polymorphism is a commonly studied DRD2\u0000gene variant whereby carriers of the low-function T allele (T/T or T/C genotypes) show\u0000reduced brain dopamine function. Therefore, individuals who have the DRD2 Taq1A polymorphism\u0000will experience higher levels of drug addiction because the T allele is associated\u0000with a reduced number of dopamine binding sites in the brain. A study of this gene\u0000has been conducted in some areas, but there is no research for the population of Indonesia.\u0000\u0000\u0000\u0000This study will focus on the frequency of the DRD2 Taq1A gene polymorphism\u0000in the population of Indonesia and define its association with drug addiction.\u0000\u0000\u0000\u0000This is a cross sectional study in which 182 subjects were divided into 91 drugaddicted\u0000patients and 91 non-drug-addicted control subjects. The genotype analysis was\u0000carried out by a modified allele-specific Polymerase Chain Reaction (PCR) method.\u0000\u0000\u0000\u0000 The frequency of the T/T and C/T was significantly higher in the addicted than\u0000control subjects. They are 6.6% and 63.7% compared to 0% and 3.3%. Likewise, the T allele\u0000is more frequent in the addicted equal to 38%, compared to only 2% in the control\u0000subjects. The frequency of the T allele between the addicted and control subjects shows a\u0000significant difference (p-value < 0.0001; 95% CI), with the addicted being at a higher risk\u0000of having the T allele (OR = 37.3; 95% CI [11.46-121.29]).\u0000\u0000\u0000\u0000There is a significant difference in the frequency of the DRD2 Taq1A gene\u0000polymorphism between addicted patients and control subjects. Thus, there is an association\u0000between this gene polymorphism and the development of drug addiction with T allele\u0000increases the predisposition to addiction.\u0000","PeriodicalId":11056,"journal":{"name":"Current Pharmacogenomics and Personalized Medicine","volume":"99 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85921491","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":"Genetic Determinants Involved in the Osteoporosis Pathophysiology","authors":"Madiha Nooreen, Shafia Fatima, R. Nagarapu, M. Khan, A. Khan","doi":"10.2174/1875692117999201211143315","DOIUrl":"https://doi.org/10.2174/1875692117999201211143315","url":null,"abstract":"\u0000\u0000Osteoporosis is a chronic disease characterized by decreased bone mass and\u0000distorted microarchitecture that leads to increased bone fragility making an individual\u0000prone to fractures. It is one of the most widely affected diseases worldwide that has the\u0000potential to cause serious morbidity, mortality and cost implications. It is a multifactorial\u0000disease that is influenced by the interaction between genetic, hormonal, nutritional and\u0000environmental factors. As it is a polygenic disorder, myriad genes influence the disease\u0000condition to a varied extent. The identification of genes or loci that effects the development\u0000of the disease will help not only in individualizing the prognosis, treatment and prevention\u0000of fractures but also in discovering novel therapeutic agents. The genetic association\u0000studies on osteoporosis have reported conflicting results. Well designed and efficiently\u0000conducted studies with enough power to detect variations in the interaction between\u0000various contributing factors of the disease in the homogenous population are needed to establish\u0000conclusive genotypic associations with the disease. The present review briefly\u0000summarizes the data published on the genes affecting osteoporosis development.\u0000","PeriodicalId":11056,"journal":{"name":"Current Pharmacogenomics and Personalized Medicine","volume":"48 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75252647","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":"Novel Somatic Mutations of the CDH1 Gene Associated with Gastric Cancer: Prediction of Pathogenicity Using Comprehensive In silico Methods","authors":"P. Chakraborty, S. Ghatak, R. Yadav, Subhajit Mukherjee, Lalchhandama Chhakchhuak, S. Chenkual, Thomas Zomuana, S. T. Lalruatfela, A. Maitra, N. S. Kumar","doi":"10.2174/1875692117999201109210911","DOIUrl":"https://doi.org/10.2174/1875692117999201109210911","url":null,"abstract":"\u0000\u0000Mutations in the CDH1 and the role of E-cadherin proteins are well\u0000established in gastric cancer. Several in silico tools are available to predict the pathogenicity\u0000of the mutations present in the genes with varying efficiency and sensitivity to detect the\u0000pathogenicity of the mutations.\u0000\u0000\u0000\u0000Our objective was to identify somatic pathogenic variants in CDH1 involved in\u0000Gastric Cancer (GC) by Sanger sequencing as well as using in silico tools and to find out\u0000the best efficient tool for pathogenicity prediction of somatic missense variants.\u0000\u0000\u0000\u0000Sanger sequencing of CDH1 was done for 80 GC tumor and adjacent normal tissues.\u0000Synthetic data sets were downloaded from the COSMIC database for comparison of\u0000the known mutations with the discovered mutations from the present study. Different algorithms\u0000were used to predict the pathogenicity of the discovery and synthetic mutation datasets\u0000using various in-silico tools. Statistical analysis was done to check the efficiency of\u0000the tools to predict pathogenic variants by using MEDCALC and GraphPad.\u0000\u0000\u0000\u0000Six missense somatic variants were found in exons 3, 4, 7, 9, 12 and 15. Out of the\u00006 variants, 5 variants (chr16:68835618C>A, chr16:68845613A>C, chr16:68847271T>G,\u0000chr16:68856001T>G, chr16:68863585G>C) were novel and not reported in disease variant\u0000databases. PROVEAN, Polyphen 2 and PANTHER predicted the pathogenicity of the variants\u0000more efficiently in both the discovery and synthetic datasets. The overall sensitivity of\u0000predictions ranged from 60 to 80%, depending on the program used, with specificity from\u000055 to 100%.\u0000\u0000\u0000\u0000This study estimates the specificity and sensitivity of prediction tools in predicting\u0000novel missense variants of CDH1 in Gastric Cancer. We report that PROVEAN,\u0000Polyphen 2 and PANTHER are efficient predictors with constant higher specificity and accuracy.\u0000This study will help the researchers to explore mutations with the best pathogenicity\u0000prediction tools.\u0000","PeriodicalId":11056,"journal":{"name":"Current Pharmacogenomics and Personalized Medicine","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79489848","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":"In Silico Study of Potential Cross-Kingdom Plant MicroRNA Based Regulation in Chronic Myeloid Leukemia","authors":"M. H. Elias, Noraziah Nordin, N. A. Hamid","doi":"10.2174/1875692118666200106113610","DOIUrl":"https://doi.org/10.2174/1875692118666200106113610","url":null,"abstract":"\u0000\u0000Chronic Myeloid Leukaemia (CML) is associated with the BCRABL1\u0000gene, which plays a central role in the pathogenesis of CML. Thus, it is crucial to\u0000suppress the expression of BCR-ABL1 in the treatment of CML. MicroRNA is known to\u0000be a gene expression regulator and is thus a good candidate for molecularly targeted therapy\u0000for CML.\u0000\u0000\u0000\u0000 This study aims to identify the microRNAs from edible plants targeting the 3’\u0000Untranslated Region (3’UTR) of BCR-ABL1.\u0000\u0000\u0000\u0000In this in silico analysis, the sequence of 3’UTR of BCR-ABL1 was obtained\u0000from Ensembl Genome Browser. PsRNATarget Analysis Server and MicroRNA Target\u0000Prediction (miRTar) Server were used to identify miRNAs that have binding conformity\u0000with 3’UTR of BCR-ABL1. The MiRBase database was used to validate the species of\u0000plants expressing the miRNAs. The RNAfold web server and RNA COMPOSER were\u0000used for secondary and tertiary structure prediction, respectively.\u0000\u0000\u0000\u0000In silico analyses revealed that cpa-miR8154, csi-miR3952, gma-miR4414-5p,\u0000mdm-miR482c, osa-miR1858a and osa-miR1858b show binding conformity with strong\u0000molecular interaction towards 3’UTR region of BCR-ABL1. However, only cpa-miR-\u00008154, osa-miR-1858a and osa-miR-1858b showed good target site accessibility.\u0000\u0000\u0000\u0000It is predicted that these microRNAs post-transcriptionally inhibit the BCRABL1\u0000gene and thus could be a potential molecular targeted therapy for CML. However,\u0000further studies involving in vitro, in vivo and functional analyses need to be carried out to\u0000determine the ability of these miRNAs to form the basis for targeted therapy for CML.\u0000","PeriodicalId":11056,"journal":{"name":"Current Pharmacogenomics and Personalized Medicine","volume":"4 1","pages":"125-132"},"PeriodicalIF":0.0,"publicationDate":"2020-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75508489","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":"Oncogenomics and CYP450 Implications in Personalized Cancer Therapy","authors":"G. K. Udayaraja, I. Emerson","doi":"10.2174/1875692117999200517122652","DOIUrl":"https://doi.org/10.2174/1875692117999200517122652","url":null,"abstract":"\u0000\u0000The Human Genome Project has unleashed the power of genomics\u0000in clinical practice as a choice of individualized therapy, particularly in cancer\u0000treatment. Pharmacogenomics is an interdisciplinary field of genomics that deals with\u0000drug response, based on individual genetic makeup.\u0000\u0000\u0000\u0000The main genetic events associated with carcinogenesis activate oncogenes or\u0000inactivate tumor-suppressor genes. Therefore, drugs should be specific to inactivate or\u0000regulate these mutant genes and their protein products for effective cancer treatment. In\u0000this review, we summarize how polymedication decisions in cancer treatments based on\u0000the evaluation of cytochrome P450 (CYP450) polymorphisms are applied for pharmacogenetic\u0000assessment of anticancer therapy outcomes.\u0000\u0000\u0000\u0000However, multiple genetic events linked, inactivating a single mutant gene product,\u0000may be insufficient to inhibit tumor progress. Thus, genomics and pharmacogenetics\u0000directly influence a patient’s response and aid in guiding clinicians to select the safest and\u0000most effective combination of medications for a cancer patient from the initial prescription.\u0000\u0000\u0000\u0000This review outlines the roles of oncogenes, the importance of cytochrome\u0000P450 (CYP450) in cancer susceptibility, and its impact on drug metabolism, proposing\u0000combined approaches to achieve precision therapy.\u0000","PeriodicalId":11056,"journal":{"name":"Current Pharmacogenomics and Personalized Medicine","volume":"14 1","pages":"104-113"},"PeriodicalIF":0.0,"publicationDate":"2020-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89468462","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":"Genomics and Pharmacogenomics of Rhinosinusitis","authors":"J. Guerra, J. Carril, M. Alcaraz, M. Santiago, L. Corzo, R. Cacabelos","doi":"10.2174/1875692117999200801024849","DOIUrl":"https://doi.org/10.2174/1875692117999200801024849","url":null,"abstract":"\u0000\u0000Polymorphisms of selected inflammatory and metabolic genes\u0000have been described in the etiology of chronic rhinosinusitis, and these effects can be explained\u0000on a pharmacogenetic basis.\u0000\u0000\u0000\u0000The purpose of this study was to examine whether there is an association between\u0000inflammatory factors and some of these alleles, by associating these genetic variables\u0000with each other.\u0000\u0000\u0000\u0000CYP1A2, CYP2D6, CYP2C19, CYP2C9, CYP3A4, CYP3A5, G6PD, NAT2,\u0000UGT1A1, VKORC1, ABCB1, SLCO1B1, APOE, TNF, IL1B, IL6 and IL6R gene polymorphisms\u0000were analyzed by PCR. Drug-metabolizing enzymes were classified according to\u0000their phenotype. Blood cell counts and biochemical parameters were also considered.\u0000\u0000\u0000\u0000Significant differences were found in the CYP1A2 phenotype, with fewer\u0000CYP1A2 normal metabolizers (NMs) expressing sinusitis (14.3% vs 30%) and a greater\u0000number of CYP1A2 ultra-rapid-metabolizers (UMs)(85% vs 69%); and in TNF, affecting\u0000TNF-A/A (4% vs 2%) and TNF-G/G (78% vs 66%) compared with TNF-G/A (19% vs\u000032%) carriers. 96% of patients with CRS had at least one G allele. When trigenic variables\u0000involved in sinusitis were analyzed, statistical differences were found in SLCO1B1-TNFCYP1A2,\u0000with a higher proportion of subjects with 1/1-GG-UM (44.3%); and IL1B-TNFCYP1A2\u0000with CC-GG-UM (26%), CT-GG-UM (19.8%) and CC-GG-NM (13.7%) genophenotypes,\u0000respectively. Subjects with sinusitis had a higher eosinophil count (308.80\u0000cel/mcL vs 263.14 cel/mcL) and lower HDL levels (265.34 vs 297.85 mg/dL).\u0000\u0000\u0000\u0000SLCO1B1-TNF-CYP1A2 and IL1B-TNF-CYP1A2 trigenic clusters may condition\u0000the chronicity of sinusitis. Eosinophilia and HDL are factors involved in inflammation,\u0000and thus in the development of CRS.\u0000","PeriodicalId":11056,"journal":{"name":"Current Pharmacogenomics and Personalized Medicine","volume":"34 1","pages":"114-124"},"PeriodicalIF":0.0,"publicationDate":"2020-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78371675","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}