Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Cases in Precision Medicine: APOL1 and Genetic Testing in the Evaluation of Chronic Kidney Disease and Potential Transplant.

ABSTRACT: This article discusses potential indications for genetic testing in an African American patient with chronic kidney disease who is being evaluated for a kidney transplant. Two known risk variants in the APOL1 (apolipoprotein L1) gene predispose to kidney disease and are found almost exclusively in persons of African ancestry. APOL1 risk variants are considered, including whether clinicians should incorporate genetic testing in the screening process for living kidney donors. In addition to APOL1 testing, the role of diagnostic exome sequencing in evaluating potential transplant recipients and donors with a positive family history of kidney disease is discussed.

SUBMITTER: Neugut YD

PROVIDER: S-EPMC7441647 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Cases in Precision Medicine: APOL1 and Genetic Testing in the Evaluation of Chronic Kidney Disease and Potential Transplant.

Neugut Y Dana YD Mohan Sumit S Gharavi Ali G AG Kiryluk Krzysztof K

Annals of internal medicine 20191008 9

This article discusses potential indications for genetic testing in an African American patient with chronic kidney disease who is being evaluated for a kidney transplant. Two known risk variants in the APOL1 (apolipoprotein L1) gene predispose to kidney disease and are found almost exclusively in persons of African ancestry. APOL1 risk variants are considered, including whether clinicians should incorporate genetic testing in the screening process for living kidney donors. In addition to APOL1 ...[more]

PMID: 31590185

Similar Datasets

Precision medicine implementation challenges for <i>APOL1</i> testing in chronic kidney disease in admixed populations.

Project description:Chronic Kidney Disease (CKD) is a public health problem that presents genetic and environmental risk factors. Two alleles in the Apolipoprotein L1 (APOL1) gene were associated with chronic kidney disease; these alleles are common in individuals of African ancestry but rare in European descendants. Genomic studies on Afro-Americans have indicated a higher prevalence and severity of chronic kidney disease in people of African ancestry when compared to other ethnic groups. However, estimates in low- and middle-income countries are still limited. Precision medicine approaches could improve clinical outcomes in carriers of risk alleles in the Apolipoprotein L1 gene through early diagnosis and specific therapies. Nevertheless, to enhance the definition of studies on these variants, it would be necessary to include individuals with different ancestry profiles in the sample, such as Latinos, African Americans, and Indigenous peoples. There is evidence that measuring genetic ancestry improves clinical care for admixed people. For chronic kidney disease, this knowledge could help establish public health strategies for monitoring patients and understanding the impact of the Apolipoprotein L1 genetic variants in admixed populations. Therefore, researchers need to develop resources, methodologies, and incentives for vulnerable and disadvantaged communities, to develop and implement precision medicine strategies and contribute to consolidating diversity in science and precision medicine in clinical practice.

| S-EPMC9797503 | biostudies-literature

Make Precision Medicine Work for Chronic Kidney Disease.

Project description:Precision medicine is based on accurate diagnosis and tailored intervention through the use of omics and clinical data together with epidemiology and environmental exposures. Precision medicine should be achieved with minimum adverse events and maximum efficacy in patients with chronic kidney disease (CKD). In this review, the breakthroughs of omics in CKD and the application of systems biology are reviewed. The potential role of transforming growth factor-?1 in the targeted intervention of renal fibrosis is discussed as an example of how to make precision medicine work for CKD.

| S-EPMC5588375 | biostudies-literature

Whole-Exome Sequencing Enables a Precision Medicine Approach for Kidney Transplant Recipients.

Project description:BackgroundWhole-exome sequencing (WES) finds a CKD-related mutation in approximately 20% of patients presenting with CKD before 25 years of age. Although provision of a molecular diagnosis could have important implications for clinical management, evidence is lacking on the diagnostic yield and clinical utility of WES for pediatric renal transplant recipients.MethodsTo determine the diagnostic yield of WES in pediatric kidney transplant recipients, we recruited 104 patients who had received a transplant at Boston Children's Hospital from 2007 through 2017, performed WES, and analyzed results for likely deleterious variants in approximately 400 genes known to cause CKD.ResultsBy WES, we identified a genetic cause of CKD in 34 out of 104 (32.7%) transplant recipients. The likelihood of detecting a molecular genetic diagnosis was highest for patients with urinary stone disease (three out of three individuals), followed by renal cystic ciliopathies (seven out of nine individuals), steroid-resistant nephrotic syndrome (nine out of 21 individuals), congenital anomalies of the kidney and urinary tract (ten out of 55 individuals), and chronic glomerulonephritis (one out of seven individuals). WES also yielded a molecular diagnosis for four out of nine individuals with ESRD of unknown etiology. The WES-related molecular genetic diagnosis had implications for clinical care for five patients.ConclusionsNearly one third of pediatric renal transplant recipients had a genetic cause of their kidney disease identified by WES. Knowledge of this genetic information can help guide management of both transplant patients and potential living related donors.

| S-EPMC6362619 | biostudies-literature

Analytical Validation of a Personalized Medicine APOL1 Genotyping Assay for Nondiabetic Chronic Kidney Disease Risk Assessment.

Project description:The incidence of chronic kidney disease (CKD) varies by ancestry, with African Americans (AA) having a threefold to fourfold higher rate than whites. Notably, two APOL1 alleles, termed G1 [c.(1072A>G; 1200T>G)] and G2 (c.1212_1217del6), are strongly associated with higher rates of nondiabetic CKD and an increased risk for hypertensive end-stage renal disease. This has prompted the opportunity to implement APOL1 testing to identify at-risk patients and modify other risk factors to reduce the progression of CKD to end-stage renal disease. We developed an APOL1 genotyping assay using multiplex allele-specific primer extension, and validated using 58 positive and negative controls. Genotyping results were completely concordant with Sanger sequencing, and both triplicate interrun and intrarun genotyping results were completely concordant. Multiethnic APOL1 allele frequencies were also determined by genotyping 7059 AA, Hispanic, and Asian individuals from the New York City metropolitan area. The AA, Hispanic, and Asian APOL1 G1 and G2 allele frequencies were 0.22 and 0.13, 0.037 and 0.025, and 0.013 and 0.004, respectively. Notably, approximately 14% of the AA population carried two risk alleles and are at increased risk for CKD, compared with <1% of the Hispanic and Asian populations. This novel APOL1 genotyping assay is robust and highly accurate, and represents one of the first personalized medicine clinical genetic tests for disease risk prediction.

| S-EPMC4816711 | biostudies-literature

Transplant Nephrologists' Preferences for Clinical Decision Support for APOL1 Genetic Testing of Living Kidney Donors: A Focus Group Study.

Project description: Not available

| S-EPMC10695637 | biostudies-literature

Cases in Precision Medicine: The Role of Pharmacogenetics in Precision Prescribing.

Project description:Pharmacogenetics may help physicians deliver individualized treatments based on how a person's genes affect a drug's effects and metabolism. This information can help prevent adverse events or improve drug efficacy by enabling the physician to optimize dosage or to avoid a medication with adverse reactions and to prescribe an alternative therapy. This article discusses the current clinical utility of pharmacogenetic testing in the context of a patient who requires anticoagulation with warfarin.

| S-EPMC7458588 | biostudies-literature

Precision Cardiovascular Medicine: State of Genetic Testing.

Project description:In the 15 years following the release of the first complete human genome sequences, our understanding of rare and common genetic variation as determinants of cardiovascular disease susceptibility, prognosis, and therapeutic response has grown exponentially. As such, the use of genomics to enhance the care of patients with cardiovascular diseases has garnered increased attention from clinicians, researchers, and regulatory agencies eager to realize the promise of precision genomic medicine. However, owing to a large burden of "complex" common diseases, emphasis on evidence-based practice, and a degree of unfamiliarity/discomfort with the language of genomic medicine, the development and implementation of genomics-guided approaches designed to further individualize the clinical management of a variety of cardiovascular disorders remains a challenge. In this review, we detail a practical approach to genetic testing initiation and interpretation as well as review the current state of cardiovascular genetic and pharmacogenomic testing in the context of relevant society and regulatory agency recommendations/guidelines.

| S-EPMC6364981 | biostudies-literature

Cervical Evaluation: From Ancient Medicine to Precision Medicine.

Project description:Since ancient times, cervical assessment for predicting timing of delivery has relied primarily on digital (subjective) assessment of dilatation, softening, and length. To date, transvaginal ultrasound cervical length is the only one of these parameters that meets criteria for a biomarker; no objective, quantitative measure of cervical dilatation or softening has gained clinical acceptance. This review discusses how the cervix has been assessed from ancient times to the present day and how a precision medicine approach could improve understanding of not only the cervix, but also parturition in general.

| S-EPMC5503468 | biostudies-literature

FHIR Genomics: enabling standardization for precision medicine use cases.

Project description:The development of Fast Healthcare Interoperability Resources (FHIR) Genomics, a feasible and efficient method for exchanging complex clinical genomic data and interpretations, is described. FHIR Genomics is a subset of the emerging Health Level 7 FHIR standard and targets data from increasingly available technologies such as next-generation sequencing. Much care and integration of feedback have been taken to ease implementation, facilitate wide-scale interoperability, and enable modern app development toward a complete precision medicine standard. A new use case, the integration of the Variant Interpretation for Cancer Consortium (VICC) "meta-knowledgebase" into a third-party application, is described.

| S-EPMC7080712 | biostudies-literature

From Genetic Testing to Precision Medicine in Epilepsy.

Project description:Epilepsy includes a number of medical conditions with recurrent seizures as common denominator. The large number of different syndromes and seizure types as well as the highly variable inter-individual response to the therapies makes management of this condition often challenging. In the last two decades, a genetic etiology has been revealed in more than half of all epilepsies and single gene defects in ion channels or neurotransmitter receptors have been associated with most inherited forms of epilepsy, including some focal and lesional forms as well as specific epileptic developmental encephalopathies. Several genetic tests are now available, including targeted assays up to revolutionary tools that have made sequencing of all coding (whole exome) and non-coding (whole genome) regions of the human genome possible. These recent technological advances have also driven genetic discovery in epilepsy and increased our understanding of the molecular mechanisms of many epileptic disorders, eventually providing targets for precision medicine in some syndromes, such as Dravet syndrome, pyroxidine-dependent epilepsy, and glucose transporter 1 deficiency. However, these examples represent a relatively small subset of all types of epilepsy, and to date, precision medicine in epilepsy has primarily focused on seizure control, and other clinical aspects, such as neurodevelopmental and neuropsychiatric comorbidities, have yet been possible to address. We herein summarize the most recent advances in genetic testing and provide up-to-date approaches for the choice of the correct test for some epileptic disorders and tailored treatments that are already applicable in some monogenic epilepsies. In the next years, the most probably scenario is that epilepsy treatment will be very different from the currently almost empirical approach, eventually with a "precision medicine" approach applicable on a large scale.

| S-EPMC7283411 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data