Influence of CMTM8 polymorphisms on lung cancer susceptibility in the Chinese Han population
Conclusion
Our study first reported that CMTM8 polymorphisms were a risk factor for lung cancer, which suggested the potential roles of CMTM8 in the development of lung cancer. (Source: Pharmacogenetics and Genomics)
Source: Pharmacogenetics and Genomics - May 1, 2021 Category: Genetics & Stem Cells Tags: Original Articles Source Type: research
Striatin genotype-based, mineralocorticoid receptor antagonist-driven clinical trial: study rationale and design
Objectives
In human studies and genetically altered mouse studies, variants in the striatin gene (STRN) are associated with increased blood pressure (BP) and aldosterone on a liberal salt diet. This clinical trial is based on the presumed mechanism for striatin-associated HTN – increased aldosterone. It is designed to determine if participants with the STRN risk alleles will have a greater BP reduction on a liberal salt diet with a specific, mechanism-based therapy – a mineralocorticoid receptor antagonist, eplerenone – as compared with a nonspecific anti-hypertensive therapy – amlodipine.
Methods
One hu...
Source: Pharmacogenetics and Genomics - May 1, 2021 Category: Genetics & Stem Cells Tags: Original Articles Source Type: research
Ligand-specific pharmacogenetic effects of nonsynonymous mutations
In pharmacogenomics, variable receptor phenotypes, resulting from genetic polymorphisms, are often described as a change in protein function or regulation observed upon exposure to a drug. However, in some instances, phenotypes are defined using a class of medications rather than individual drugs. This paradigm assumes that a variation associated with a drug response phenotype will retain the magnitude and direction of the effect for other drugs with the same mechanism of action. However, nonsynonymous polymorphisms may have ligand-specific effects. The purpose of this study was to investigate the potential for point mutat...
Source: Pharmacogenetics and Genomics - May 1, 2021 Category: Genetics & Stem Cells Tags: Mini Review Source Type: research
A pilot study to investigate the utility of NAT2 genotype-guided isoniazid monotherapy regimens in NAT2 slow acetylators
Isoniazid is a therapeutic agent for the treatment of latent tuberculosis infection. Genetic variants in the N-acetyltransferase 2 (NAT2) are associated with the safety and pharmacokinetics of isoniazid. The study aimed to evaluate the safety and pharmacokinetics of a NAT2 genotype-guided regimen of isoniazid monotherapy. A randomized, open-label, parallel-group and multiple-dosing study was performed in healthy subjects. The subjects received isoniazid for 29 days. The NAT2 slow acetylators (NAT2*5/*5, -*5/*6, -*5/*7, -*6/*6, -*6/*7, -*7/*7) randomly received standard dose (300 mg, standard-treatment group) or reduced d...
Source: Pharmacogenetics and Genomics - March 11, 2021 Category: Genetics & Stem Cells Tags: Short Communication Source Type: research
JMJD1C knockdown affects myeloid cell lines proliferation, viability, and gemcitabine/carboplatin-sensitivity
This study investigates if JMJD1C knockdown affects gemcitabine/carboplatin-sensitivity in cell lines.
Methods
Lentiviral transduction-mediated shRNA knockdown of JMJD1C in the cell lines K562 and MEG-01 were performed using shRNA#32 and shRNA#33. The knockdown was evaluated using qPCR. Cell proliferation, viability, and gemcitabine/carboplatin-sensitivity were subsequently determined using cell counts, trypan blue, and the MTT assay.
Results
ShRNA#33 resulted in JMJD1C downregulation by 56.24% in K562 and 68.10% in MEG-01. Despite incomplete knockdown, proliferation (reduction of cell numbers by 61–68%, da...
Source: Pharmacogenetics and Genomics - March 11, 2021 Category: Genetics & Stem Cells Tags: Original Articles Source Type: research
HCP5 rs2395029 is a rapid and inexpensive alternative to HLA-B*57:01 genotyping to predict abacavir hypersensitivity reaction in Spain
In this study, we aimed to assess the linkage disequilibrium between HCP5 rs2395029 and HLA-B*57:01 in patients receiving medical assistance at our hospital. We selected 226 HIV-infected patients from our hospital who had been routinely genotyped since 2009 with the SSOP and Sanger sequencing method: 49 HLA-B*57:01 positives and 177 negatives. We genotyped them for HCP5 rs2395019 by real time PCR (qPCR). We exploratory performed two copy number variation assays flanking HCP5 rs2395019 to explore possible deletions that could break the linkage disequilibrium with HLA-B*57:01. The concordance between HLA-B*57:01 and the HCP5...
Source: Pharmacogenetics and Genomics - March 11, 2021 Category: Genetics & Stem Cells Tags: Original Articles Source Type: research
Race and smoking status associated with paclitaxel drug response in patient-derived lymphoblastoid cell lines
The use of ex-vivo model systems to provide a level of forecasting for in-vivo characteristics remains an important need for cancer therapeutics. The use of lymphoblastoid cell lines (LCLs) is an attractive approach for pharmacogenomics and toxicogenomics, due to their scalability, efficiency, and cost-effectiveness. There is little data on the impact of demographic or clinical covariates on LCL response to chemotherapy. Paclitaxel sensitivity was determined in LCLs from 93 breast cancer patients from the University of North Carolina Lineberger Comprehensive Cancer Center Breast Cancer Database to test for potential associ...
Source: Pharmacogenetics and Genomics - January 6, 2021 Category: Genetics & Stem Cells Tags: Short Communication Source Type: research
Association between polymorphisms in the vitamin D receptor and susceptibility to multiple sclerosis
Conclusions
The VDR FokI (rs2228570) polymorphism was significantly associated with developing MS. We found no influence of the ApaI (rs7975232), BsmI (rs1544410), Cdx2 (rs11568820), FokI (rs2228570), and TaqI (rs731236) gene polymorphisms on the risk of developing MS in our patients. (Source: Pharmacogenetics and Genomics)
Source: Pharmacogenetics and Genomics - January 6, 2021 Category: Genetics & Stem Cells Tags: Original Articles Source Type: research
Identification of high-impact gene–drug pairs for pharmacogenetic testing in Alberta, Canada
Conclusions
We uncovered specific patterns in drug dispensing and identified important gene–drug pairs that will inform the planning and development of an evidenced-based PGx testing service in Alberta, Canada. Adaptation of our approach may facilitate the process of evidence-based PGx testing implementation in other jurisdictions. (Source: Pharmacogenetics and Genomics)
Source: Pharmacogenetics and Genomics - January 6, 2021 Category: Genetics & Stem Cells Tags: Original Articles Source Type: research
Pharmacogenetic interactions of rifapentine plus isoniazid with efavirenz or nevirapine
Conclusions
Among HIV-positive individuals receiving efavirenz or nevirapine, and who then initiated rifapentine plus isoniazid in A5279, NAT2 slow acetylators had greater rifapentine and 25-desacetyl rifapentine concentrations, and greater increases from baseline in plasma efavirenz and nevirapine concentrations. These associations are likely mediated by greater isoniazid exposure in NAT2 slow acetylators. (Source: Pharmacogenetics and Genomics)
Source: Pharmacogenetics and Genomics - November 7, 2020 Category: Genetics & Stem Cells Tags: Original Articles Source Type: research
Role of enterocyte-specific gene polymorphisms in response to adjuvant treatment for stage III colorectal cancer
Conclusions
Our findings suggest that MS4A12 and CDX2 gene polymorphisms may predict outcome in stage III CRC. However, the clinical significance of SNPs for response to oxaliplatin may differ by tumor stage. (Source: Pharmacogenetics and Genomics)
Source: Pharmacogenetics and Genomics - November 7, 2020 Category: Genetics & Stem Cells Tags: Original Articles Source Type: research
Single-nucleotide polymorphism biomarkers of adjuvant anastrozole-induced estrogen suppression in early breast cancer
Conclusions
We identified a SNP-based model that had excellent performance characteristics for predicting the phenotype of elevated E1 and E2 in women treated with anastrozole. This model was not validated in an independent dataset but that dataset was clinically and genomically substantially different. The model will need validation in a prospective study. (Source: Pharmacogenetics and Genomics)
Source: Pharmacogenetics and Genomics - November 7, 2020 Category: Genetics & Stem Cells Tags: Original Articles Source Type: research
Association of SLCO1B1 c.521T>C (rs4149056) with discontinuation of atorvastatin due to statin-associated muscle symptoms
The most common adverse drug reaction from statins are statin-associated muscle symptoms (SAMS), characterized by myopathy (weakness), myalgia (muscle pain), and commonly elevation in serum creatine kinase. All statins are substrates of the organic anion transporter 1B1 (OATP1B1; gene: SLCO1B1), albeit to different degrees. A genetic polymorphism in SLCO1B1, c.521T>C (rs4149056), markedly decreases OATP1B1 function. The literature is currently unclear as to whether SLCO1B1 c.521T>C is significantly associated with discontinuation of atorvastatin specifically due to SAMS. Our hypothesis was that individuals carrying the SLC...
Source: Pharmacogenetics and Genomics - October 3, 2020 Category: Genetics & Stem Cells Tags: Short Communication Source Type: research
Methods and implementation of a pediatric asthma pharmacogenomic study in the emergency department setting
Conclusions
Pharmacogenomic studies can be conducted in the ED setting, and enroll a younger patient population with a high proportion of minority participants. By disseminating this study’s methods and feasibility analysis, we aim to increase interest in pharmacogenomic studies set in the ED and aimed toward future ED-based pharmacogenomic decision-making. (Source: Pharmacogenetics and Genomics)
Source: Pharmacogenetics and Genomics - October 3, 2020 Category: Genetics & Stem Cells Tags: Original Articles Source Type: research
Patient insights on features of an effective pharmacogenomics patient portal
Conclusions
Patients named providers as their primary source of pharmacogenomic information, but a pharmacogenomics patient portal that is carefully constructed to incorporate desired features may be a favorable tool to effectively deliver pharmacogenomic information and results to patients. (Source: Pharmacogenetics and Genomics)
Source: Pharmacogenetics and Genomics - October 3, 2020 Category: Genetics & Stem Cells Tags: Original Articles Source Type: research
