Journal of Pharmacogenomics and Pharmacoproteomics最新文献

{"title":"Pharmacogenomics of CYP3A5 Polymorphism: Predicting Dose-adjustedTrough Levels of Tacrolimus in South Indian Renal Transplant Patients","authors":"S. Sreeja, N. Gracious, R. Nair, S. Nair","doi":"10.4172/2153-0645.1000161","DOIUrl":"https://doi.org/10.4172/2153-0645.1000161","url":null,"abstract":"Tacrolimus is a potent immunosuppressant clinically used for the long term treatment of antirejection of transplanted organs in liver and kidney transplant recipients although dose optimization is often poorly managed. So far, no study has been carried out in the South Indian kidney transplant patients. The objective of this study was to evaluate the potential influence of a functional polymorphism in CYP3A5*3 gene on tacrolimus physiological availability/dose ratio in South Indian renal transplant patients. Twenty five renal transplant recipients receiving tacrolimus were enrolled in this study. Their body weight, drug dosage, and therapeutic concentration of tacrolimus were observed. All patients were on a standard immunosuppressive regime of tacrolimus-mycophenolate mofetil (Immunosuppressant) along with steroids at a starting dose of 0.1 mg/kg/day tacrolimus. CYP3A5 genotyping was performed by PCR followed with RFLP. Confirmation of RFLP analysis and variation in the nucleotide sequence of CYP3A5*3 gene were determined by direct sequencing using a validated automated genetic analyzer. A significant association was found between tacrolimus dose/kg/d and CYP3A5 gene (A6986G) polymorphism in the study population. The CYP3A5 *1/*1,*1/*3 and *3/*3 genotypes were detected in 5 (20%), 5 (20%) and 15 (60%) of the 25 graft recipients, respectively. CYP3A5*3 genotypes were found to be a good predictor of tacrolimus Level/Dose (L/D) ratio in kidney transplant recipients. Significantly higher L/D ratios were observed among non-expressors 9.483 ng/mL (range 4.5-14.1 ng/mL) as compared with the expressors 5.154 ng/mL (range 4.42-6.5 ng/mL) of CYP3A5. Biopsy Proven Acute Rejection (BPAR) episodes were significantly higher in CYP3A5*1 homozygotes compared to patients with CYP3A5*1/*3 and CYP3A5*3/*3 genotypes (40% vs. 20% and 13%, respectively). The dosenormalized tacrolimus concentration (ng/mL/mg/Kg) was significantly lower in patients having CYP3A5*1/*3 polymorphism. This is the first study to extensively determine the effect of CYP3A5*3 genetic polymorphism on tacrolimus pharmacokinetics in South Indian renal transplant recipients, and this study also showed that the majority of our patients carry mutant allele A6986G in the CYP3A5*3 gene. Identification of CYP3A5 polymorphism prior to transplantation is important for selecting the appropriate initial dosage of tacrolimus for each patient.","PeriodicalId":333396,"journal":{"name":"Journal of Pharmacogenomics and Pharmacoproteomics","volume":"9 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2016-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"116457907","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":"Towards a Comprehensive Understanding of miRNA Regulome andmiRNA Interaction Networks","authors":"Joseph Nalluri, D. Barh, V. Azevedo, P. Ghosh","doi":"10.4172/2153-0645.1000160","DOIUrl":"https://doi.org/10.4172/2153-0645.1000160","url":null,"abstract":"miRNAs are vital regulators of post transcriptional gene expression. Deregulation of miRNAs lead to susceptibility towards many diseases, especially cancers. Their complicated molecular mechanisms comprising of upstream transcriptions factors, downstream targets, functional and biological processes, and disease regulations are not fully comprehended yet. Hence, understanding the miRNA regulatory network comprehensively is pivotal to modulate its functions and develop miRNA therapeutics. At present, several independent databases and tools containing specific information about parts of a miRNA regulome exist in silo which prevents a holistic understanding of miRNA's molecular mechanism. Hence, integration of all scattered datasets in a cohesive manner in order to get an overarching understanding of the contributory influence and the effluence from the machinery of a miRNA regulome is critical. In this article, we present a case-report on miRegulome, a first comprehensive integrated knowledge base of miRNA regulome and miRNA interaction network analytic tools. miRegulome integrates the essential molecular modules of a miRNA regulome into a cohesive platform. We also discuss miRNA-disease interactions from miRegulome and devise graph theoretical strategies to analyze them. We also present a next-level design for an enhanced database repository for comprehensive data analysis collating diverse datasets related to miRNA biology; and present the need and challenges for the development of novel algorithms to predict new interactions between miRNAs, genes, transcription factors and diseases.","PeriodicalId":333396,"journal":{"name":"Journal of Pharmacogenomics and Pharmacoproteomics","volume":"56 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2016-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"128079895","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 Proteomics of Virulent, Avirulent and Drug ResistantStrains of Tuberculous Mycobacteria","authors":"B. Harinath, Lingaraja Jena, G. Wankhade, Pranita J Waghmare","doi":"10.4172/2153-0645.1000159","DOIUrl":"https://doi.org/10.4172/2153-0645.1000159","url":null,"abstract":"Mycobacterium tuberculosis (MTB), the causal organism of the oldest infectious disease tuberculosis is the leading cause of morbidity and mortality worldwide. This pathogenic organism has been evolved into variety of strains with diverse genotype, phenotype and pathogenic properties such as MTB H37Rv and CDC1551 strains which are virulent, while MTB H37Ra is an a virulent strain and MTB KZN strain is resistant to different antituberculosis drugs. Due to the advancement in genome sequencing and molecular biology, whole genomes of different MTB strains have been completely sequenced. Genomic as well as proteomic comparison among the sequenced strains will help in understanding the differences between virulent, a virulent and resistant organisms. This article reviews the information available on completely sequenced MTB strains and presents the studies reported by researchers on genomic and proteomic comparison of various MTB strains.","PeriodicalId":333396,"journal":{"name":"Journal of Pharmacogenomics and Pharmacoproteomics","volume":"13 1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2016-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"133142288","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":"MicroRNAs Role in the Central Nervous System Development andAbnormalities","authors":"Fang Liu, Cheng Wang","doi":"10.4172/2153-0645.1000E154","DOIUrl":"https://doi.org/10.4172/2153-0645.1000E154","url":null,"abstract":"Initially, non-coding RNAs were thought to be “junk RNAs”. MicroRNAs (miRNAs), a group of small non-coding RNA molecules, were discovered in 1993 [1,2]. However, their functions have been found to be associated with diverse biological procedures, including development, metabolism, immunity, hematopoietic differentiation, etc. [3]. It is estimated that miRNAs regulate the activity of approximately 60% of human protein-coding genes [4]. Abnormal miRNA expression may lead to a number of diseases, such as neoplasms [5,6], age-related diseases [7], and neurological disorders [8]. Advances in miRNA research have suggested that miRNAs not only help to understand molecular mechanisms of human CNS diseases, but also have potential to serve as biomarkers for early detection of neurological and/or neurodegenerative alterations.","PeriodicalId":333396,"journal":{"name":"Journal of Pharmacogenomics and Pharmacoproteomics","volume":"33 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2016-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"125933912","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":"New Concept of Bipolar Disorders","authors":"Lu, Chia-Ling Li, Yi-Lun Chung","doi":"10.4172/2153-0645.1000E152","DOIUrl":"https://doi.org/10.4172/2153-0645.1000E152","url":null,"abstract":"1Department of Psychiatry, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan 2Institute of Behavioral Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan 3Institute of Allied Health Sciences, College of Medicine and Hospital, National Cheng Kung University, Tainan, Taiwan 4Addiction Research Center, National Cheng Kung University, Tainan, Taiwan 5Institute of Basic Medical Sciences, National Cheng Kung University, Tainan, Taiwan 6Center for Neuropsychiatric Research, National Health Research Institutes, Miaoli, Taiwan *Correspondence author: Ru-Band Lu, Department of Psychiatry, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan, E-mail: rblu@mail.ncku.edu.tw","PeriodicalId":333396,"journal":{"name":"Journal of Pharmacogenomics and Pharmacoproteomics","volume":"2 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2016-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"131376202","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":"Epigenetic Modifications: Are we Closer to Clinical Applicability?","authors":"F. Ponchel, A. Burska","doi":"10.4172/2153-0645.1000158","DOIUrl":"https://doi.org/10.4172/2153-0645.1000158","url":null,"abstract":"Epigenetics encompass all inheritable, although potentially reversible changes in the genome, that do not alter the DNA code, but result from both developmentally (ensuring tissue specificity) and environmentally (resulting for exposure to many factors) driven modification of the spatial conformation of the DNA through chemical modification of the nucleotide chain itself or of the chromatin associated proteins. Epigenetic controls gene expression at a higher level than transcription, imputing on the genome an environmental signature that is heritable through cell division and reflects a life-long experience. These types of modification (particularly DNA methylation patterns) explain phenotypic differences between identical twins. As opposed to genetic mutation, these modifications are reversible and are controlled by groups of enzymes (the epigenetic machinery, DNA methyltransferases (DNMT), histone deacetylases (HDACs) and histone acetyl transferases (HATs) and many more), hence, epigenetic marks include DNA methylation, histone modification and nucleosome positioning resulting in higher structural organisation of the chromatin regulating gene expression at the level of DNA accessibility for the transcriptional machinery to bind and initiate transcription.","PeriodicalId":333396,"journal":{"name":"Journal of Pharmacogenomics and Pharmacoproteomics","volume":"36 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2016-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"121378690","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":"The Prevalence of Rare Variants Potentially Important for the Response to Medicines Used for CVD Treatment in the Lithuanian Population","authors":"A. Pranculis, T. RanÄelis, L. AmbrozaitytÄ, I. UktverytÄ, I. DomarkienÄ, N. BurokienÄ, KuÄinskienÄ Za, KuÄinskas","doi":"10.4172/2153-0645.1000157","DOIUrl":"https://doi.org/10.4172/2153-0645.1000157","url":null,"abstract":"Cardiovascular disease (CVD) is one of the leading causes of death among Europeans and around the world. Major factors that are considered relevant for the efficacy or adverse drug reactions (ADRs) caused by drugs used for CVD treatment have been identified through GWAS studies mostly using low density common variant genotyping arrays. In this study whole exome sequencing (WES) was carried out to identify genomic variants relevant for CVD treatment. The study group included 98 (49 males and 49 females) self-reported healthy unrelated individuals from the Lithuanian population with at least three generations of Lithuanian ethnicity and residency in the same ethnolinguistic region. After performing WES genetic loci of 55 genes that were reported as relevant to the efficacy or ADRs caused by drugs used for CVD treatment were analyzed using LifeScopeTM and ANNOVAR software. The analysis of small indels in the selected regions revealed 13 exonic frameshift indels and a single intronic splice site variant that may affect the efficacy or cause ADRs in patients treated for CVD. Over 400 potentially relevant SNVs in different frequencies were detected in the genes reported to be important for CVD treatment. The strength of evidence analysis identified 14 SNVs most likely to be relevant for CVD treatment. The frequency distribution of several variant alleles that have been shown to be highly important for CVD treatment in the CYP2D6 (rs16947) and ADRB1 (rs1801253) as well as several variants in the CYP2C9 and NAT2 genes were determined to be significantly (p<0.05) different from other Caucasian populations showing the potential benefit of pharmacogenomic testing prior to treatment in the Lithuanian population. The research was carried out under the LITGEN project. LITGEN project (VP1-3.1-SMM-07-K-01-013) was funded by the European Social Fund under the Global Grant measure.","PeriodicalId":333396,"journal":{"name":"Journal of Pharmacogenomics and Pharmacoproteomics","volume":"32 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2016-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"115711127","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":"Non-Coding RNAs: A Dynamic and Complex Network of Gene Regulation","authors":"A. Munshi, Mohan, Y. Ahuja","doi":"10.4172/2153-0645.1000156","DOIUrl":"https://doi.org/10.4172/2153-0645.1000156","url":null,"abstract":"It has been estimated that less than two percent of the mammalian genome encodes proteins, rest of the genome which was earlier considered as junk DNA is the treasure trove of non-coding RNAs (ncRNAs). Many ncRNAs have now been characterized. They constitute one of the largest families of gene regulators that are found in plants and animals. They form a complex network and have key roles in diverse regulatory pathways involved in human health and disease. In this review, different types of ncRNAs, their biogenesis, structure, function and evolutionary significance is showcased","PeriodicalId":333396,"journal":{"name":"Journal of Pharmacogenomics and Pharmacoproteomics","volume":"64 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2016-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"126255534","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":"Prediction of 5-Fluorouracil Toxicity Associated With Dihydropyrimidine Dehydrogenase Gene (DPYD) Polymorphism Using the Secondary Structure Prediction Programs","authors":"K. Son","doi":"10.4172/2153-0645.1000154","DOIUrl":"https://doi.org/10.4172/2153-0645.1000154","url":null,"abstract":"5-fluorouracil (5-FU) is rapidly degraded by dihydropyrimidine dehydrogenase (DPD), the first and rate-limiting enzyme in the catabolic pathway of 5-FU and pyrimidines. A tolerable therapeutic dose of 5-FU for a DPD-normal patient can make a DPD-deficient patient intolerable. These inter-individual variations in the body’s response and tolerance to drugs can be attributed to dihydropyrimidine dehydrogenase gene (DPYD) single nucleotide polymorphisms (SNPs), among others. To save a patient’s life and money, health professionals need a convenient and reliable way to find out a patient’s tolerance to 5-FU prior to clinical trials or 5-FU therapy. Here I present a simple, easy and fast way to predict an individual’s intolerance to 5-FU using the secondary structure prediction programs, YASPIN, PSIPRED and Jpred 3, freely available to anyone. These programs predict the DPD secondary structure with and without mutation (s) within DPYD so that an impact of the mutation-induced structural changes on functional sites of human DPD domains can be deduced. Among 11 SNPs analyzed as samples, two missense mutations, D949V (SNP A2846T) and C953S (SNP G2858C), in the DPD domain V are predicted to cause disruption of the domain core responsible for [4Fe-4S] clusters. Furthermore, a point mutation in a splicing region (In 14 G1A) in DPYD is predicted to produce truncated DPD mRNAs (exon 14 skipping) and disabled DPD proteins (missing 55 amino acids from D581 to N635) which cause a complete loss of DPD activity. SWISS-MODEL predicts significant change in the three dimensional structures of human DPD in the presence of exon 14 skipping, D949V and C953S mutation. Thus, prediction by these secondary structure prediction programs provides useful and reliable information about toxicity associated 5-FU due to mutation (s) in DPYD.","PeriodicalId":333396,"journal":{"name":"Journal of Pharmacogenomics and Pharmacoproteomics","volume":"16 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2015-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"125742825","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":"Biological Properties and Antioxidant Activity of Hawthorn Crataegus mexicana","authors":"eras-Tarabay Jose Antonio, Cervantes-Rodríguez Margarita, Méndez-Iturbide Daniel","doi":"10.4172/2153-0645.1000153","DOIUrl":"https://doi.org/10.4172/2153-0645.1000153","url":null,"abstract":"The traditional fruit in Mexico represent a great variety of species with nutritious properties and with a wide field of usage in traditional medicine. “Tejocote” (hawthorn) is a fruit with medicinal properties since pre-hispanic times due to its high content of Vitamin A, Vitamin C, minerals, oligomeric procianidines, triterpenes, carotenes, flavonoids, polysaccharides and catecholamines. Some of these compounds are used to treat cardiovascular diseases, as well as immune diseases and respiratory problems such as colds and cough, neurological problems, eye disease, reproductive organs disease, and in the liver and kidneys, since “tejocote” has citotoxic activity, gastro protective, anti-inflammatory, anti-viral and anti-microbian. The current review is focused on the botanical features, ethnobotanical and phytochemical of the “tejocote” from the gender Crataegus mexicana, which is the variety grown and most consumed in our country. There are very few studies concerning its contents of metabolites, its potential use as anti-oxidant and its applications in order to treat some diseases.","PeriodicalId":333396,"journal":{"name":"Journal of Pharmacogenomics and Pharmacoproteomics","volume":"16 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2015-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"116802876","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}