Journal of translational genetics and genomics最新文献

{"title":"Genomics and precision medicine in pediatric acute lymphoblastic leukemia","authors":"R. Santiago, T. Tran","doi":"10.20517/jtgg.2021.16","DOIUrl":"https://doi.org/10.20517/jtgg.2021.16","url":null,"abstract":"Acute lymphoblastic leukemia (ALL) is the most frequent malignant disease in the pediatric population, accounting for about 25% of childhood cancers. Drastic therapeutic improvements have been made for pediatric ALL since the early 1960s, marking the most successful treatment paradigm in pediatric oncology. The clinical success derived from refined risk-adapted therapy based on presenting features, cytogenetics and minimal residual disease, prevention of central nervous system relapse, and improvement of supportive care measures. With contemporary therapies, survival of children with ALL now exceeds 90%. However, ALL represents one of leading causes of cancer-related death, as 15%-20% of patients continue to relapse and outcomes post-relapse remain poor. Since the early 2000s, large-scale genomic studies of ALL, greatly facilitated by the advent of next generation sequencing (NGS), have enabled the development of a novel taxonomy for ALL in the molecular era. The access to NGS technologies identifies novel ALL subsets characterized by “driver” oncogenic alterations, previously cryptic on conventional karyotyping methods. With genomic characterization, the group of formerly unclassified B-lineage ALL reduces from 25% to a marginal 5% of ALL. The revised molecular classification of ALL confers prognostic significance and describes the predilection of unfavorable ALL subtypes with increasing age, partially elucidating the worst outcome of adolescents and young adults with ALL. Large-scale genomic analysis also reveals inherited alterations predisposing to ALL occurrence or to different drugs’ sensitivities. Most importantly, the genomic portrait of ALL uncovers novel therapeutic vulnerabilities, paving the way towards precision medicine opportunities Page 381 Santiago et al. J Transl Genet Genom 2021;5:380-95 https://dx.doi.org/10.20517/jtgg.2021.16","PeriodicalId":73999,"journal":{"name":"Journal of translational genetics and genomics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67658372","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":"Kava root extracts hinder prostate cancer development and tumorigenesis by involvement of dual inhibition of MAO-A and LSD1.","authors":"Xuesen Li,&nbsp;Liankun Song,&nbsp;Shan Xu,&nbsp;Matthew Tippin,&nbsp;Shuan Meng,&nbsp;Jun Xie,&nbsp;Edward Uchio,&nbsp;Xiaolin Zi","doi":"10.20517/jtgg.2021.22","DOIUrl":"https://doi.org/10.20517/jtgg.2021.22","url":null,"abstract":"<p><strong>Aim: </strong>Here, we aim to evaluate the chemopreventive efficacy of kava root extracts (KRE) in transgenic adenocarcinoma of the mouse prostate (TRAMP) mice and investigate potential molecular targets of kavalactones, the main components of kava.</p><p><strong>Methods: </strong>TRAMP mice were administrated with KRE formulated food for different periods of time, and then the incidences of high-grade prostatic intraepithelial neoplasia (HG-PIN) and adenocarcinomas and tumor burdens were compared between vehicle control and KRE food fed groups. In addition, the inhibitory effect of the KRE and kavalactones on monoamine oxidase A (MAO-A) and lysine-specific demethylase 1 (LSD1) enzyme activities were examined by commercially available inhibitor screening kits. Histone H3 lysine 9 dimethylation was also evaluated in prostate cancer cells and tumor tissues using Western blotting analysis.</p><p><strong>Results: </strong>Dietary feeding of 0.3% and 0.6% KRE to TRAMP mice from ages of 6 weeks to 12 weeks inhibited HG-PIN by 43.5% and 59.7%, respectively, and prostate adenocarcinoma by 53.5% and 66.4%, respectively. In addition, 0.6% KRE fed TRAMP mice from ages of 6 weeks to 24 weeks exhibited a significant reduction of genitourinary weight (a surrogate of tumor burden) by 54.5% and reduced body weight gain. Furthermore, the KRE and kavalactones showed a significant inhibition of LSD1 and MAO-A enzyme activities.</p><p><strong>Conclusion: </strong>Our results suggest that consumption of kava products through diet can delay prostate cancer development and progression and that kavalactones may be a new structure model for developing a potent dual inhibitor of LSD1 and MAO-A.</p>","PeriodicalId":73999,"journal":{"name":"Journal of translational genetics and genomics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8341175/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10755951","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 effect of HMGB1 and RAGE on the clinicopathological and prognostic features of prostate cancer","authors":"D. Lv","doi":"10.20517/jtgg.2021.34","DOIUrl":"https://doi.org/10.20517/jtgg.2021.34","url":null,"abstract":"As a DNA-binding protein, high mobility group box 1 (HMGB1) has been shown be involved in various biological activities, including transcription regulation, DNA repair, genomic stability, and extracellular signaling. Accumulating evidence indicates that HMGB1 has an important role in biological processes in cancer. Moreover, HMGB1 has been shown to have intracellular and extracellular roles, activating key cancerogenic signaling pathways. The main signal pathway is activated via the interaction of HMGB1 with its receptor, receptor for advanced glycation end-products (RAGE). In addition, overexpression of HMGB1/RAGE occurs in certain types of primary tumors and has been linked to increased metastasis and poorer prognosis. In our previous research, we demonstrated that co-expression of HMGB1 and RAGE is associated with cancer progression and poor patient outcome in prostate cancer (PCa). Together with the recent published evidence, we describe and speculate on the character of the HMGB1/RAGE axis in PCa progression and elaborate on future prospects for the application of potential strategies to target HMGB1 in PCa therapy.","PeriodicalId":73999,"journal":{"name":"Journal of translational genetics and genomics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67658452","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":"Shared genomic segment analysis in a large high-risk chronic lymphocytic leukemia pedigree implicates <i>CXCR4</i> in inherited risk.","authors":"Julie E Feusier, Michael J Madsen, Brian J Avery, Justin A Williams, Deborah M Stephens, Boyu Hu, Afaf E G Osman, Martha J Glenn, Nicola J Camp","doi":"10.20517/jtgg.2021.05","DOIUrl":"10.20517/jtgg.2021.05","url":null,"abstract":"<p><strong>Aim: </strong>Chronic lymphocytic leukemia (CLL) has been shown to cluster in families. First-degree relatives of individuals with CLL have an ~8 fold increased risk of developing the malignancy. Strong heritability suggests pedigree studies will have good power to localize pathogenic genes. However, CLL is relatively rare and heterogeneous, complicating ascertainment and analyses. Our goal was to identify CLL risk loci using unique resources available in Utah and methods to address intra-familial heterogeneity.</p><p><strong>Methods: </strong>We identified a six-generation high-risk CLL pedigree using the Utah Population Database. This pedigree contains 24 CLL cases connected by a common ancestor. We ascertained and genotyped eight CLL cases using a high-density SNP array, and then performed shared genomic segment (SGS) analysis - a method designed for extended high-risk pedigrees that accounts for heterogeneity.</p><p><strong>Results: </strong>We identified a genome-wide significant region (<i>P</i> = 1.9 × 10^-7, LOD-equivalent 5.6) at 2q22.1. The 0.9 Mb region was inherited through 26 meioses and shared by seven of the eight genotyped cases. It sits within a ~6.25 Mb locus identified in a previous linkage study of 206 small CLL families. Our narrow region intersects two genes, including <i>CXCR4</i> which is highly expressed in CLL cells and implicated in maintenance and progression.</p><p><strong>Conclusion: </strong>SGS analysis of an extended high-risk CLL pedigree identified the most significant evidence to-date for a 0.9 Mb CLL disease locus at 2q22.1, harboring <i>CXCR4.</i> This discovery contributes to a growing literature implicating <i>CXCR4</i> in inherited risk to CLL. Investigation of the segregating haplotype in the pedigree will be valuable for elucidating risk variant(s).</p>","PeriodicalId":73999,"journal":{"name":"Journal of translational genetics and genomics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8341589/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39292871","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":"Novel imaging technologies for genetic diagnoses in the inborn errors of metabolism","authors":"A. Gropman, Afrouz A. Anderson","doi":"10.20517/jtgg.2020.09","DOIUrl":"https://doi.org/10.20517/jtgg.2020.09","url":null,"abstract":"Many inborn errors of metabolism and genetic disorders affect the brain. The brain biochemistry may differ from that in the periphery and is not accessible by simple blood and urine sampling. Therefore, neuroimaging has proven to be a valuable tool to not only evaluate the brain structure, but also biochemistry, blood flow and function. Neuroimaging in patients with inborn errors of metabolism can include additional sequences in addition to T1 and T2-weighted imaging because in early stages, there may be no significant findings on the routine sequnces due to the lack of sensitivity or the evolution of abnormalities lags behind the ability of the imaging to detect it. In addition, findings on T1 and T2-weighted imaging of several inborn errors of metabolism may be non-specific and be seen in other non-genetic conditions. Therefore, additional neuroimaging modalities that have been employed including diffusion tensor imaging (DTI), magnetic resonance spectroscopy, functional MRI (fMRI), functional near infrared spectroscopy (fNIRS), or positron emission tomography (PET) imaging may further inform underlying changes in myelination, biochemistry, and functional connectivity. The use of Magnetic Resonance Spectroscopy in certain disorders may add a level of specificity depending upon the metabolite levels that are abnormal, as well as provide information about the process of brain injury (i.e., white matter, gray matter, energy deficiency, toxic buildup or depletion of key metabolites). It is even more challenging to understand how genetic or metabolic disorders contribute to short and/or long term changes in cognition which represent the downstream effects of IEMs. In order to image “cognition” or the downstream effects of a metabolic disorder on domains of brain function, more advanced techniques are required to analyze underlying fiber tracts or alternatively, methods such as fMRI enable generation of brain activation maps after both task based and resting state conditions. DTI can be used to look at changes in white matter tracks. Each imaging modality can explore an important aspect of the anatomy, physiology or biochemisty of the central nervous system. Their properties, pros and cons are discussed in this article. These imaging modalities will be discussed in the context of several inborn errors of metabolism including Galactosemia, Phenylketonruia, Maple syrup urine disease, Methylmalonic acidemia, Niemann-Pick Disease, type C1, Krabbe Disease, Ornithine transcarbamylase deficiency, Sjogren Larsson syndrome, Pelizeaus-Merzbacher disease, Pyruvate dehydrogenase deficiency, Nonketotic Hyperglycinemia and Fabry disease. Space constraints do not allow mention of all the disorders in which one of these modalities has been investigated, or where it would add value to diagnosis or disease progression.","PeriodicalId":73999,"journal":{"name":"Journal of translational genetics and genomics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42780711","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 genes and variants associated with longevity in Bulgarian centenarians revealed by whole exome sequencing DNA pools: a pilot study","authors":"D. Serbezov, L. Balabanski, S. Karachanak-Yankova, R. Vazharova, D. Nesheva, Zora Hammoudeh, R. Staneva, Marta Mihaylova, V. Damyanova, O. Antonova, D. Nikolova, S. Hadjidekova, D. Toncheva","doi":"10.20517/jtgg.2020.41","DOIUrl":"https://doi.org/10.20517/jtgg.2020.41","url":null,"abstract":"Aim: To determine specific genetic loci that might be associated with longevity in Bulgarian population by analyzing exome pool-seq data from centenarians and a control group. Methods: We performed whole-exome sequencing of two DNA pools, set up of 32 Bulgarian centenarians and 61 young healthy controls, respectively, and 59935 quality filtered variants were concurrently detected in both pools. Fisher’s exact test was employed to establish the significance of allele frequency difference between the pools. Results: Forty seven variants showed significantly higher allele frequency in the centenarian compared to the control pool, and these can be considered to be positively associated with longevity in Bulgarian populaton. Based on their assigned functional role, three genes containing three of these variants were further investigated. These genes, RNF43 , WNK1 and NADSYN1 , are involved in evolutionary conserved processes with well ascertained association with longevity, i.e., Wnt signaling pathway, insulin/IGF-1 signal pathway and redox balancing processes, respectively. For the remaining genes exhibiting variants with significantly higher allele frequency in the Serbezov et al. J Transl Genet Genom 2020;4:446-54 I http://dx.doi.org/10.20517/jtgg.2020.41 Page 447 Bulgarian centenarian pool there is not enough evidence about their functional role in determining longevity and further research is needed. Conclusion: The results confirm the importance of studying centenarians in different populations to discover those combinations of variants that associate with longer health span.","PeriodicalId":73999,"journal":{"name":"Journal of translational genetics and genomics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47352653","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":"Advancement in the diagnosis of mitochondrial diseases","authors":"S. A. Sulaiman, Zam Zureena Mohd Rani, Fara Zela Mohd Radin, N. A. Murad","doi":"10.20517/jtgg.2020.27","DOIUrl":"https://doi.org/10.20517/jtgg.2020.27","url":null,"abstract":"Mitochondrial diseases are multi-systemic, heterogeneous groups of diseases that are associated with various neuromuscular problems, cardiovascular disorders, metabolic syndrome, cancer, and obesity. Mitochondrial diseases are due to mutations in mitochondrial DNA or nuclear DNA that can affect the assembly of the mitochondrial components and mitochondrial function. Typically, mitochondrial diseases can be inherited through an autosomal dominant, autosomal recessive or X-linked pattern of inheritance. To date, there are more than 100 mitochondrial diseases identified. However, clinical phenotype heterogeneity is a huge problem for the diagnosis of mitochondrial diseases, as patients with the same mutations exhibit different clinical symptoms. Also, the heteroplasmy/homoplasmy conditions complicate the diagnosis process. Here, in this review, we discuss these challenges and problems in mitochondrial disease diagnosis, focusing on the mutational profile of both primary and secondary mitochondrial diseases. We also review the utilization of next-generation technology and multi-omics strategy to improve the diagnosis. The discussion addresses the current evidence of those applications and the challenges that need some improvement for better diagnosis yield.","PeriodicalId":73999,"journal":{"name":"Journal of translational genetics and genomics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75953378","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":"Mitochondrial neurogastrointestinal encephalomyopathy: approaches to diagnosis and treatment.","authors":"Bridget E Bax","doi":"10.20517/jtgg.2020.08","DOIUrl":"https://doi.org/10.20517/jtgg.2020.08","url":null,"abstract":"<p><p>Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is an ultra-rare disease caused by mutations in <i>TYMP,</i> the gene encoding for the enzyme thymidine phosphorylase. The resulting enzyme deficiency leads to a systemic accumulation of thymidine and 2'-deoxyuridine and ultimately mitochondrial failure due to a progressive acquisition of secondary mitochondrial DNA (mtDNA) mutations and mtDNA depletion. MNGIE is characterised by gastrointestinal dysmotility, cachexia, peripheral neuropathy, ophthalmoplegia, ptosis and leukoencephalopathy. The disease is progressively degenerative and leads to death at an average age of 37.6 years. Patients invariably encounter misdiagnoses, diagnostic delays, and non-specific clinical management. Despite its rarity, MNGIE has invoked much interest in the development of therapeutic strategies, mainly because it is one of the few mitochondrial disorders where the molecular abnormality is metabolically and physically accessible to manipulation. This review provides a resume of the current diagnosis and treatment approaches and aims to increase the clinical awareness of MNGIE and thereby facilitate early diagnosis and timely access to treatments, before the development of untreatable and irreversible organ damage.</p>","PeriodicalId":73999,"journal":{"name":"Journal of translational genetics and genomics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7116056/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38366570","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 North American mitochondrial disease registry.","authors":"Xiomara Q Rosales,&nbsp;John L P Thompson,&nbsp;Richard Haas,&nbsp;Johan L K Van Hove,&nbsp;Amel Karaa,&nbsp;Danuta Krotoski,&nbsp;Kristin Engelstad,&nbsp;Richard Buchsbaum,&nbsp;Salvatore DiMauro,&nbsp;Michio Hirano","doi":"10.20517/jtgg.2020.12","DOIUrl":"https://doi.org/10.20517/jtgg.2020.12","url":null,"abstract":"<p><strong>Aim: </strong>The North American Mitochondrial Disease Consortium (NAMDC) comprises a network of 17 clinical centers with a mission to conduct translational research on mitochondrial diseases. NAMDC is a part of the Rare Disease Clinical Research Network (RDCRN) and is funded by the National Institutes of Health. To foster its mission, NAMDC has implemented a comprehensive Mitochondrial Disease Clinical Registry (hereafter NAMDC Registry), collected biosamples deposited into the NAMDC Biorepository, defined phenotypes and genotypes of specific disorders, collected natural history data, identified outcome measures, characterized safety and long-term toxicity and efficacy of promising therapies, and trained young investigators interested in patient-oriented research in mitochondrial disease.</p><p><strong>Methods: </strong>Research conducted by NAMDC is built on the foundation of the Clinical Registry. Data within the registry are encrypted and maintained in a centralized database at Columbia University Medical Center. In addition to clinical data, NAMDC has established a mitochondrial disease biorepository, collecting DNA, plasma, cell, and tissue samples. Specimens are assigned coded identifiers in compliance with all relevant regulatory entities and with emerging NIH guidelines for biorepositories. NAMDC funds two pilot projects each year. Pilot grants are small grants typically supporting an early stage concept to obtain preliminary data. Pilot grants must enhance and address major issues in mitochondrial medicine and specific areas of need for the field and for the successful outcome of NAMDC. The grant selection process is facilitated by input from multiple stakeholders including patient organizations and the strategic leadership of NAMDC. To train new mitochondrial disease investigators, NAMDC has established a Fellowship Program which offers a unique training opportunity to senior postdoctoral clinical fellows. The fellowship includes a 6-month period of intensive training in clinical trial methodology through the Clinical Research Enhancement through Supplemental Training program and equivalent programs at the other sites, along with rotations up to 3 months each to two additional consortium sites where a rich and varied training experience is provided. Nine core educational sites participate in this training program, each offering a summer grant program in mitochondrial medicine funded by our NAMDC partner the United Mitochondrial Disease Foundation (www.umdf.org). All clinical research in NAMDC depends on the participation of mitochondrial disease patients. Since individual mitochondrial disorders are often extremely rare, major communication and recruitment efforts are required. Therefore, NAMDC has forged a very close partnership with the premier patient advocacy group for mitochondrial diseases in North America, the United Mitochondrial Disease Foundation (UMDF).</p><p><strong>Results: </strong>The NAMDC Registry has confir","PeriodicalId":73999,"journal":{"name":"Journal of translational genetics and genomics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7323997/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38099206","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 review of the pharmacogenomics of buprenorphine for the treatment of opioid use disorder.","authors":"Hemanuel Arroyo Seguí, Kyle Melin, Darlene Santiago Quiñones, Jorge Duconge","doi":"10.20517/jtgg.2020.35","DOIUrl":"10.20517/jtgg.2020.35","url":null,"abstract":"<p><p>As the opioid epidemic continues to grow across the United States, the number of patients requiring treatment for opioid use disorder continues to climb. Although medication-assisted treatment presents a highly effective tool that can help address this epidemic, its use has been limited. Nonetheless, with easier dosing protocols (compared to the more complex dosing required of methadone due to its long and variable half-life) and fewer prescribing limitations (may be prescribed outside the setting of federally approved clinics), the increase in buprenorphine use in the United States has been dramatic in recent years. Despite buprenorphine's demonstrated efficacy, patient-specific factors can alter the response to the medications, which may lead to treatment failure in some patients. Clinical characteristics (sex, concurrent medications, and mental health comorbidities) as well as social determinants of health (housing status, involvement with the criminal justice system, and socioeconomic status) may impact treatment outcomes. Furthermore, a growing body of data suggests that genetic variations can alter pharmacological effects and influence therapeutic response. This review will cover the available pharmacogenomic data for the use of buprenorphine in the management of opioid use disorders. Pharmacogenomic determinants that affect opioid receptors, the dopaminergic system, metabolism of buprenorphine, and adverse events are discussed. Although much of the existing data comes from observational studies, clinical research is ongoing. Nevertheless, the development of pharmacogenomic-guided strategies has the potential to reduce opioid misuse, improve clinical outcomes, and save healthcare resources.</p>","PeriodicalId":73999,"journal":{"name":"Journal of translational genetics and genomics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7709797/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38672375","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}